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Methods for Molecular Replacement

Grzegorz Chojnowski gave a lecture "Methods underlying extension of MR solutions in ARP/wARP" at the CCP4 Study Weekend "Molecular Replacement", held on 8-10 January 2019 at the University of Nottingham, UK


ARP/wARP around the world

The group members participated in several international workshops and training schools for young pre- and postdoctoral researchers the last quarter of 2018.

It was again a busy time for Grzegorz Chojnowski, he gave a number of lectures and hands-on practical tutorials for ARP/wARP at:
  • CCP4 School in Macromolecular Crystallography, Chandigarh, India, October 2018
  • IFSC/CCP4 Macromolecular Crystallography School Workshop in São Carlos, Brazil, November 2018
  • DLS/CCP4 Data Collection and Analysis Workshop. Didcot, United Kingdom, December 2018

Sravya Kantamneni and Egor Sobolev lectured and demonstrated ARP/wARP at:
  • CCP4/Spring-8 Workshop. Osaka, Japan, October 2018


Announcement of ARP/wARP 8.0 at the EMBL News

The major ARP/wARP software release 8.0 was published at the EMBL EtCetera. The software now includes first-ever online tool for building cryo-EM macromolecular models from scratch


Release of ARP/wARP 8.0

The ARP/wARP developers, jointly with the CCP4 core team, released the long-awaited for the next-generation ARP/wARP software version 8.0. The software incorporates key developments made over the years 2016-2018 including the novel approaches for sequence-docking and building disordered loops. The performance for macromolecular model building has been considerably improved at resolutions within 2.0-3.5 Å for X-ray crystallography and ARP/wARP is now capable of de novo interpretation of cryo-EM maps.


New trainee joins the group

Koushik Choudhury has joined our group as a trainee, to work on his Master's thesis until 15 April 2019. Koushik's project addresses the challenges of automated macromolecular model building at medium resolution of the data through the exploitation of structural information present in the Protein Data Bank.


ARP/wARP for EM presented at 31st European Crystallography Meeting in Oviedo

Grzegorz Chojnowski presented the new ARP/wARP module for building atomic models of macromolecules at the 31st European Crystallography Meeting. The module is already available with the latest ARP/wARP version 8.0 and on our Webservice.


ARP/wARP around the world

Grzegorz Chojnowski presents ARP/wARP at the CCP4/APS Macromolecular Crystallography School


New paper published with Hakanpää J, Hackenberg C and Lamzin VS

Structural and functional insights into the unique CBS-CP12 fusion protein family in cyanobacteria.
Hackenberg C, Hakanpaa J, Cai F, Antonyuk S, Eigner C, Meissner S, Laitaoja M, Janis J, Kerfeld CA, Dittmann E, Lamzin VS
Cyanobacteria are important photosynthetic organisms inhabiting a range of dynamic environments. This phylum is distinctive among photosynthetic organisms in containing genes encoding uncharacterized cystathionine beta-synthase (CBS)-chloroplast protein (CP12) fusion proteins. These consist of two domains, each recognized as stand-alone photosynthetic regulators with different functions described in cyanobacteria (CP12) and plants (CP12 and CBSX). Here we show that CBS-CP12 fusion proteins are encoded in distinct gene neighborhoods, several unrelated to photosynthesis. Most frequently, CBS-CP12 genes are in a gene cluster with thioredoxin A (TrxA), which is prevalent in bloom-forming, marine symbiotic, and benthic mat cyanobacteria. Focusing on a CBS-CP12 from Microcystis aeruginosa PCC 7806 encoded in a gene cluster with TrxA, we reveal that the domain fusion led to the formation of a hexameric protein. We show that the CP12 domain is essential for hexamerization and contains an ordered, previously structurally uncharacterized N-terminal region. We provide evidence that CBS-CP12, while combining properties of both regulatory domains, behaves different from CP12 and plant CBSX. It does not form a ternary complex with phosphoribulokinase (PRK) and glyceraldehyde-3-phosphate dehydrogenase. Instead, CBS-CP12 decreases the activity of PRK in an AMP-dependent manner. We propose that the novel domain architecture and oligomeric state of CBS-CP12 expand its regulatory function beyond those of CP12 in cyanobacteria.
Proc Natl Acad Sci U S A. 2018 Jul 3;115(27):7141-7146. doi: 10.1073/pnas.1806668115. Epub 2018 Jun 18.   PUBMED


The recent advances of the ARP/wARP software project

Victor Lamzin attended the CCP4 developers meeting in Abington, UK, and presented the ARP/wARP advances


ARP/wARP for EM presented at DGK Annual Meeting in Essen, Germany

Grzegorz Chojnowski presented the new ARP/wARP module for de novo building of atomic models of macromolecules in cryo-EM maps at the 26th Annual Meeting of the German Crystallographic Society (DGK) in Essen. The module has also been made available within our new ARP/wARP web service.


Modern challenges in constructing atomic macromolecular models from X-ray diffraction and cryo-elctron microscopy

Catch up with Victor Lamzin at the group leader (pink) seminar at the EMBL in Heidelberg to know more about challenges in building macromolecular models.


ARP/wARP in first CCP4-Israel workshop: CCP4/BGU 2018 presented the CCP4 developers meeting in Abington

For the first time, ARP/wARP team along with CCP4 team participated in a workshop in Beer-Sheba, Israel. Sravya gave a talk and tutorial on Automated model building in ARP/wARP in this workshop.


New paper published with Kallio J, Hackenberg C and Lamzin VS.

Structure and function of the N-terminal domain of the yeast telomerase reverse transcriptase.
Petrova OA, Mantsyzov AB, Rodina EV, Efimov SV, Hackenberg C, Hakanpaa J, Klochkov VV, Lebedev AA, Chugunova AA, Malyavko AN, Zatsepin TS, Mishin AV, Zvereva MI, Lamzin VS, Dontsova OA, Polshakov VI
The elongation of single-stranded DNA repeats at the 3'-ends of chromosomes by telomerase is a key process in maintaining genome integrity in eukaryotes. Abnormal activation of telomerase leads to uncontrolled cell division, whereas its down-regulation is attributed to ageing and several pathologies related to early cell death. Telomerase function is based on the dynamic interactions of its catalytic subunit (TERT) with nucleic acids-telomerase RNA, telomeric DNA and the DNA/RNA heteroduplex. Here, we present the crystallographic and NMR structures of the N-terminal (TEN) domain of TERT from the thermotolerant yeast Hansenula polymorpha and demonstrate the structural conservation of the core motif in evolutionarily divergent organisms. We identify the TEN residues that are involved in interactions with the telomerase RNA and in the recognition of the 'fork' at the distal end of the DNA product/RNA template heteroduplex. We propose that the TEN domain assists telomerase biological function and is involved in restricting the size of the heteroduplex during telomere repeat synthesis.
Nucleic Acids Res. 2018 Feb 16;46(3):1525-1540. doi: 10.1093/nar/gkx1275.   PUBMED


ARP/wARP around the world

The ARP/wARP team was present at several workshops and training schools. It was a busy year for Grzegorz Chojnowski, he presented ARP/wARP at:
  • CCP4/Spring-8 Workshop. Osaka, Japan, January 2017
  • CCP4/APS School in Macromolecular Crystallography, Advanced Photon Source, USA, June 2017
  • DLS/CCP4 Data Collection and Analysis Workshop. Didcot, United Kingdom, December 2017
  • Macromolecular Crystallography School in Montevideo, Uruguay, November 2017


First single particle experiment at European XFEL

We are excited to having joined an international collaboration that just finished the first single particle experiment at the European XFEL in Hamburg!


LASEROMIX:Final Annual meeting of the Laseromix project

Laseromix (Science and Technology Platform for Biology with X-ray Free-Electron Lasers) is a R&D project jointly funded by the German and Russian Ministries for Science and Education. Laseromix brings together experts from EMBL, University OsnabrЭck and Moscow - including Moscow State University and Kurchatov center - to develop methods to exploit the remarkable potential for measuring 3D structures and dynamics of single bioparticles using Free Electron Lasers. Laseromix will standardise protocols for sample preparation, invent novel sample delivery methods consuming very low amounts of sample and most prominently will develop software tools to process the XFEL data and enable their biological interpretation. The Laseromix project is coordinated by Victor Lamzin - EMBL-Hamburg (German side) and Natalia Novikova - National Research Center Kurchatov Moscow (Russian side)

At the final project meeting organised by the Osnabrueck project partner the group members made the following oral presentations:
  • Grzegorz Chojnowski: Crystallography using Free Electron Lasers
  • Egor Sobolev: Assembling a 3D continuous diffraction pattern of a symmetrical object from XFEL images using multidimensional scaling.


Dipcheck Webservice

We announce the DipCheck Webservice for validation of backbone geometry in protein structures as described in:
The Webservice is available at:


New paper published by Pereira J and Lamzin VS.

A distance geometry-based description and validation of protein main-chain conformation.
Pereira J, Lamzin VS
Understanding the protein main-chain conformational space forms the basis for the modelling of protein structures and for the validation of models derived from structural biology techniques. Presented here is a novel idea for a three-dimensional distance geometry-based metric to account for the fine details of protein backbone conformations. The metrics are computed for dipeptide units, defined as blocks of C(alpha)i-1-O i-1-C(alpha)i -O i -C(alpha)i+1 atoms, by obtaining the eigenvalues of their Euclidean distance matrices. These were computed for approximately 1.3 million dipeptide units collected from nonredundant good-quality structures in the Protein Data Bank and subjected to principal component analysis. The resulting new Euclidean orthogonal three-dimensional space (DipSpace) allows a probabilistic description of protein backbone geometry. The three axes of the DipSpace describe the local extension of the dipeptide unit structure, its twist and its bend. By using a higher-dimensional metric, the method is efficient for the identification of C(alpha) atoms in an unlikely or unusual geometrical environment, and its use for both local and overall validation of protein models is demonstrated. It is also shown, for the example of trypsin proteases, that the detection of unusual conformations that are conserved among the structures of this protein family may indicate geometrically strained residues of potentially functional importance.
IUCrJ. 2017 Aug 8;4(Pt 5):657-670. doi: 10.1107/S2052252517008466. eCollection 2017 Sep 1.   PUBMED


ARP/wARP around the world; IUCr 2017 in India

Meet Sravya at the IUCr 2017 (21-28.08.207) in Hyderabad. She will present ARP/wARP in satellite meeting, software fayre and poster sessions.


New ARP/wARP Webservice

We are happy to announce a redesigned and extended webservice for remote ARP/wARP execution. In addition to the crystallographic protein chain tracing, many other functionalities of ARP/wARP are now also available online. These include:
  • classic protein model building starting from phases or from existing model
  • secondary structure building
  • nucleotide building
  • solvent modelling
  • ligand modelling and identification

The webservice offers a registration with an email address, which provides more options to the users. For example, all jobs a user has previously submitted are now in one place, can be easily evaluated, compared or run again with different parameters.
The webservice is using the current ARP/wARP version 7.6.1, which has been jointly released with the CCP4 software.


New paper published by Beshnova DA, Pereira J and Lamzin VS.

Estimation of the protein-ligand interaction energy for model building and validation.
Beshnova DA, Pereira J, Lamzin VS
Macromolecular X-ray crystallography is one of the main experimental techniques to visualize protein-ligand interactions. The high complexity of the ligand universe, however, has delayed the development of efficient methods for the automated identification, fitting and validation of ligands in their electron-density clusters. The identification and fitting are primarily based on the density itself and do not take into account the protein environment, which is a step that is only taken during the validation of the proposed binding mode. Here, a new approach, based on the estimation of the major energetic terms of protein-ligand interaction, is introduced for the automated identification of crystallographic ligands in the indicated binding site with ARP/wARP. The applicability of the method to the validation of protein-ligand models from the Protein Data Bank is demonstrated by the detection of models that are `questionable' and the pinpointing of unfavourable interatomic contacts.
Acta Crystallogr D Struct Biol. 2017 Mar 1;73(Pt 3):195-202. doi: 10.1107/S2059798317003400. Epub 2017 Mar 6.   PUBMED


New paper published with Beshnova DA, and Lamzin VS.

Synthesis, SAR and molecular docking study of novel non-beta-lactam inhibitors of TEM type beta-lactamase.
Antipin RL, Beshnova DA, Petrov RA, Shiryaeva AS, Andreeva IP, Grigorenko VG, Rubtsova MY, Majouga AG, Lamzin VS, Egorov AM
The novel classes of acylated phenoxyanilide and thiourea compounds were investigated for their ability to inhibit TEM type beta-lactamase enzyme. Two compounds 4g and 5c reveal the inhibition potency in micromolar range and show their action by non-covalent binding in the vicinity of the TEM-171 active site. The structure activity relationship around carbon chain length and different substituents in ortho- and para-positions of acylated phenoxyanilide as well as molecular modelling study has been performed.
Bioorg Med Chem Lett. 2017 Apr 1;27(7):1588-1592. doi: 10.1016/j.bmcl.2017.02.025. Epub 2017 Feb 16.   PUBMED


ARP/wARP around the world

The ARP/wARP team was present at several workshops and training schools. Grzegorz Chiojnowski was attending the:
  • CCP4/APS School in Macromolecular Crystallography, Advanced Photon Source, USA, June 2016
  • DLS/CCP4 School in Macromolecular Crystallography, Diamond Light Source, UK, December 2016


Congratulations to Dr. Pereira!

Joana succeeded with defending her PhD thesis today! Congratulations.


New paper published with Beshnova DA, Kallio J, Hackenberg C and Lamzin VS.

Novel non-beta-lactam inhibitor of beta-lactamase TEM-171 based on acylated phenoxyaniline.
Grigorenko VG, Andreeva IP, Rubtsova MY, Deygen IM, Antipin RL, Majouga AG, Egorov AM, Beshnova DA, Kallio J, Hackenberg C, Lamzin VS
The microbial resistance to antibiotics is a genuine global threat. Consequently, a search of new inhibitors remains of acute importance due to the increasing spread of multidrug resistance. Here we present a new type of non-beta-lactam beta-lactamase inhibitor PA-34 based on natural phenoxyaniline, identified using computer-assisted screening of scaffolds related to those of known low-affinity inhibitors. The compound displays reversible competitive inhibition of bacterial beta-lactamase TEM-171, with a Ki of 88 muM. Using enzyme kinetics, infra-red spectroscopy, fluorescence quenching and computer docking, we propose that the inhibitor binds at the entrance to the enzyme active site. This is a novel inhibition mechanism compared to binding covalently to the catalytic serine in the active site or non-covalently to the allosteric site. The residues involved in binding the inhibitor are conserved among molecular class A beta-lactamases. The identified compound and its proposed binding mode may have a potential for a regulation of the catalytic activity of a wide range of class A beta-lactamases. We also hypothesise that the presented route for finding non-beta-lactam compounds may be an effective and durable approach for combating bacterial antibiotic resistance.
Biochimie. 2017 Jan;132:45-53. doi: 10.1016/j.biochi.2016.10.011. Epub 2016 Oct 19.   PUBMED


New group member!

Sravya Mounika Kantamneni has joined our group as a PhD student. Sravya will develop methods addressing the improvement of crystallographic phases.


New group member!

Egor Sobolev has joined our group. Egor will develop methods for the interpretation of continuous scattering from single particles for the processing of XFEL experimental data.


Release of ARP/wARP 7.6

ARP/wARP 7.6 provides improved performance in protein chain tracing, particularly at resolution below 2.5 A, as well as in DNA/RNA fragment building.

Protein model building
  • Dipeptide conformational space is introduced for the selection of the chain path
  • NCS restraints are now default at resolution 1.5 A or lower
  • Side chain fit is improved with additional real-space refinement
  • Check for java is introduced and the use of conditional restraints is turned off if java is not installed (can occur on OSX 10.10 and 10.11).

DNA/RNA building
  • The tracing of the nucleotide chain tracing is enhanced with the addition of the second algorithm for phosphate detection
  • Chain tracing now proceeds in 5-cycle iterative manner, as for the protein chain tracing

Solvent building
  • Default density thresholds for atom update are optimised

Other changes
  • ARP/wARP installer is made more robust



We take part in the West-Life project (H2020) starting today. West-Life provides services for computation and data management to researchers in structural biology, integrating multiple approaches and experimental techniques. It builds on European e-Infrastructure solutions from EGI and EUDAT and links together web services and repositories for structural biology. It is also engaged in the development and dissemination of best practices.


New group member!

Grzegorz Chojnowski has joined our group. Grzegorz will develop model building methods for CryoEM and low resolution X-ray data.


New group member!

Umut Oezugurel has joined our group as a senior technical officer. Umut will be responsible for maintenance of ARP/wARP and the implementation of novel developments into ARP/wARP. Welcome Umut!


Release of ARP/wARP 7.5

As of today the most recent ARP/wARP version (7.5) can be downloaded from This release is bundled with the ccp4 6.5 release.

Major changes in Version 7.5
  • Increased performance of protein model building through:
  • improved polypeptide recognition,
  • NCS-restraints,
  • atom update,
  • SAD-refinement option,
  • estimation of solvent content
  • and model accuracy

  • Improved stability of beta-strand, DNA/RNA and solvent building
  • "Fit Ligand" incorporates 84 most common ligands now and
  • uses cif files defining bond, torsion and plane restraints
  • Incremental improvements in auto-depth view and menus of ArpNavigator


LASEROMIX: Established new international collaborational R&D project

We established the new R&D project Laseromix bringing together experts from EMBL, University Osnabrück and Moscow - including Moscow State University and Kurchatov center - to develop methods to exploit the remarkable potential for measuring 3D structures and dynamics of single bioparticles using Free Electron Lasers. Laseromix will standardise protocols for sample preparation, invent novel sample delivery methods consuming very low amounts of sample and most prominently will develop the first comprehensive software package to process the XFEL data and enable their biological interpretation.


EMBL Labday

Taking part in the EMBL Labday 2014 and presenting "Construction and validation of macromolecular models"


New paper published by C. Carolan and V. S. Lamzin

Automated identification of crystallographic ligands using sparse-density representations.
Carolan CG, Lamzin VS
A novel procedure for the automatic identification of ligands in macromolecular crystallographic electron-density maps is introduced. It is based on the sparse parameterization of density clusters and the matching of the pseudo-atomic grids thus created to conformationally variant ligands using mathematical descriptors of molecular shape, size and topology. In large-scale tests on experimental data derived from the Protein Data Bank, the procedure could quickly identify the deposited ligand within the top-ranked compounds from a database of candidates. This indicates the suitability of the method for the identification of binding entities in fragment-based drug screening and in model completion in macromolecular structure determination.
Acta Crystallogr D Biol Crystallogr. 2014 Jul;70(Pt 7):1844-53. doi: 10.1107/S1399004714008578. Epub 2014 Jun 29.   PUBMED


New paper published by O. A. Petrova, E. M. Smekalova, M.E. Zvereva, V. Lamzin, O. A. Dontsova.

Identification of additional telomerase component of the yeast H. polymorpha is a step towards understanding the complex at the atomic level.
Petrova OA, Smekalova EM, Zvereva ME, Lamzin V, Dontsova OA
no abstract available
Dokl Biochem Biophys. 2014 Mar;455(1):59-64. doi: 10.1134/S1607672914020057. Epub 2014 May 3.   PUBMED


New paper published by N. Ponomarenko, S. D. Chatziefthimiou SD, [...], V. Lamzin, [...], A. Gabibov.

Role of kappa-->lambda light-chain constant-domain switch in the structure and functionality of A17 reactibody.
Ponomarenko N, Chatziefthimiou SD, Kurkova I, Mokrushina Y, Mokrushina Y, Stepanova A, Smirnov I, Avakyan M, Bobik T, Mamedov A, Mitkevich V, Belogurov A Jr, Fedorova OS, Dubina M, Golovin A, Lamzin V, Friboulet A, Makarov AA, Wilmanns M, Gabibov A
The engineering of catalytic function in antibodies requires precise information on their structure. Here, results are presented that show how the antibody domain structure affects its functionality. The previously designed organophosphate-metabolizing reactibody A17 has been re-engineered by replacing its constant kappa light chain by the lambda chain (A17lambda), and the X-ray structure of A17lambda has been determined at 1.95 A resolution. It was found that compared with A17kappa the active centre of A17lambda is displaced, stabilized and made more rigid owing to interdomain interactions involving the CDR loops from the VL and VH domains. These VL/VH domains also have lower mobility, as deduced from the atomic displacement parameters of the crystal structure. The antibody elbow angle is decreased to 126 degrees compared with 138 degrees in A17kappa. These structural differences account for the subtle changes in catalytic efficiency and thermodynamic parameters determined with two organophosphate ligands, as well as in the affinity for peptide substrates selected from a combinatorial cyclic peptide library, between the A17kappa and A17lambda variants. The data presented will be of interest and relevance to researchers dealing with the design of antibodies with tailor-made functions.
Acta Crystallogr D Biol Crystallogr. 2014 Mar;70(Pt 3):708-19. doi: 10.1107/S1399004713032446. Epub 2014 Feb 15.   PUBMED


New group member!

Daria Beshnova has joined our group as a new EIPOD-Postdoc. Daria is working on software development for ligand identification within the ARP/wARP software project.


Release of ARP/wARP 7.4

As of today the most recent ARP/wARP version (7.4) can be downloaded from This release will also be bundled with the upcoming ccp4 6.4.

Major changes in Version 7.4
  • The use of non-crystallographic symmetry for protein chain tracing has been further improved. On average, the built protein models are now 5% more complete and the built fragments are 50% longer. The NCS order is automatically adjusted according to the expected solvent content.
  • An alpha version of a new algorithm called Faked Data has been introduced, which additionally improves protein model building at a resolution around 2.5-3.0 Å.
  • Rfree set (0 or 1) is recognised automatically.
  • New checks are introduced to interpret the input amino-acid sequence. Additionally, on Mac OSX the sequence given in rich-text format can now be interpreted.
  • The accuracy of the estimation of the model correctness has been improved from an error of 3.0 to 2.5%.
  • The algorithm for fitting partial ligands into an electron density (cocktail screening) has been replaced with a new method that applies a number of sophisticated features and considers multiple conformations of the ligand fragments.
  • ARP/wARP identifies and fits more ligands into a specified electron density, with the protocols being faster and more sophisticated. 84 of the most common ligands in the PDB, including typically-encountered coenzymes, buffer constituents and cryo-protectant compounds are screened in all conformations against a user-defined density cluster and the best-fitting compound modelled. The protocol is conveniently and intuitively accessible from the ARP Navigator interface.
  • ARP/wARP now utilises cif files that define bond, torsion and plane restraints for ligand fitting.
  • The three-letter PDB code for a ligand can be provided as an input to ligand building via CCP4i instead of a PDB structure.
  • The ARP/wARP CCP4i interface has been extended to accommodate accumulated developments.
  • The ARP Navigator has been made more robust, the default appearance and object rastering have been made nicer. The software now works seamlessly on Mac OSX 10.8.
  • To ensure a smoother user experience, the "Quick Action"-Menu in ARP Navigator has been considerably improved. Additionally, a new button 'Submit to ViCi' has been added (ViCi is a new web-server for in-silico ligand-based drug design).
  • Supported computer platforms are Mac Intel (10.5 to 10.8) and Linux (both 32 and 64-bit versions).
  • The ARP/wARP installer has been considerably modified and became more robust. There is no need anymore to source ARP/wARP setup files in .cshrc/bash_profile. By sourcing the CCP4 setup ARP/wARP the settings to source ARP/wARP will be installed automatically for the following login shells: csh, tcsh, sh, bash, zsh.
  • CCP4 6.4.0 and Refmac 5.7.0032 (or higher) are the recommended versions to use with ARP/wARP 7.4.


Ciaran got EMBL Outstanding Postdoc Award

From the EMBL&cetera newsletter:
Five finalists presented research in areas including evolutionary biology, cancer genomics and structural biology. Selected by participants, Ciaran Carolan (Lamzin group) won, with his talk exploring the discovery and testing of novel b-Lactam inhibitors. "It's an honour to receive this award, which also recognises the important contributions to the project by EMBL colleagues and our collaborators in Moscow," said Ciaran.


Tim got the Warren DeLano Structural Bioinformatics and Computational Biophysics award

From the EMBL&cetera newsletter:
Breaking down complex science to something as simple as cats and dogs is no easy task. EMBL Hamburg postdoc Tim Wiegels wowed judges at the 3DSIG satellite meeting at this year's ISMB conference by doing just that, scooping the Warren DeLano Structural Bioinformatics and Computational Biophysics award for his presentation exploring bioinformatics methods to improve structural models in X-ray crystallography. "Using something so simple to explain pattern recognition - essentially the transformation of signals to meaning using available knowledge - grabs peoples' attention and can help them to understand better: for example, you know that pugs look different than French bulldogs and if you see a shadow with pointy ears, it's easy to deduce which dog fits," says Tim. "I am delighted the judges have recognised something that I have enjoyed doing for a long time now."


Made it to the title!

Latest ArpNavigator paper became title of Acta D (Volume 69, Part 4 (April 2013))!


ARP/wARP around the world

The ARP/wARP team will be present at several upcomming workshops and schools again:

Ciaran Carolan will be at MMX School 2013 "From data processing to structure refinement and beyond" in Montevideo, Uruguay (April 9th-17th, 2013)

Tim Wiegels will be at the APS Data collection workshop and CCP4 school: From data collection to structure refinement and beyond; June 18 - June 26 2013 in Chicago, USA


New paper published by G. G. Langer, S. Hazledine, T. Wiegels, C. Carolan and V. S. Lamzin

Visual automated macromolecular model building.
Langer GG, Hazledine S, Wiegels T, Carolan C, Lamzin VS
Automated model-building software aims at the objective interpretation of crystallographic diffraction data by means of the construction or completion of macromolecular models. Automated methods have rapidly gained in popularity as they are easy to use and generate reproducible and consistent results. However, the process of model building has become increasingly hidden and the user is often left to decide on how to proceed further with little feedback on what has preceded the output of the built model. Here, ArpNavigator, a molecular viewer tightly integrated into the ARP/wARP automated model-building package, is presented that directly controls model building and displays the evolving output in real time in order to make the procedure transparent to the user.
Acta Crystallogr D Biol Crystallogr. 2013 Apr;69(Pt 4):635-41. doi: 10.1107/S0907444913000565. Epub 2013 Mar 14.   PUBMED


New group member!

Joana Pereira has joined our group as a new predoc. Joana is working on software development within the ARP/wARP software project.


ARP/wARP around the world

Meet us at the CCP4 Study Weekend (3 - 5 January 2013) in Nottingham!


ViCi for ligand-based drug screening now online

EMBL Hamburg's new software for ligand-based drug screening, ViCi, is now live and accessible to the general community at the following webpage:

ViCi is an innovative software for ligand-based drug design available free of charge to academic researchers via this webserver. ViCi uses a combination of mathematical descriptors of molecular size, shape and topology to describe small molecule structures. Following input of a template molecule, typically that of a known ligand in its bound conformation in a particular protein, the software will rapidly screen a database (currently 8 million compounds) and extract those predicted to have similar shape and electrostatic compositions and therefore to be possible ligands for the same protein. Results are typically obtained in a matter of hours and are returned to the user ranked by probability of binding.


New group member!

Claudia Hackenberg has joined our group as a new postdoc. Claudia will strengthen our wet lab work, in particular with respect to the development of new techniques for XFEL related sample handling and preparation.


ARP/wARP around the world

Meet us at the ECM in Bergen (6-11.08.2012): Presentations by Tim and Ciaran on recent novel developments within ARP/wARP; Meet us in person at the CCP4 info booth!
  • 08.08.: 11:20; Ciaran Carolan - Automated Identification of Ligands in Macromolecular Electron Density Maps
  • 9.8.: 15:30; Tim Wiegels - Software Fayre
  • 10.08.: 11:00; Tim Wiegels - Structural bioinformatics incorporated into ARP/wARP model building
  • Poster MS7-P1 Discovery of Novel Inhibitors of Bacterial beta-Lactamases using ARP/wARP-based Drug Design
  • Poster MS49-P3 The ARP/wARP model building suite and the Arpnavigator user interface.


New group member!

Ioan Vancea has joined our group as a software developer. Ioan will be responsible for maintenance of ARP/wARP and the implementation of novel developments into ARP/wARP. Welcome Ioan!


Impact factor of 12.6 for Acta Crystallographica Section D Biological Crystallography

Thomson Reuters have released their 2011 Journal Citation Reports, where Acta Crystallographica Section D Biological Crystallography leads the crystallography rankings with its highest ever impact factor of 12.6. This is a marked success of structural biology, and is a reward of many EMBL-Hamburg employees who publish in this journal or cite the papers published therein. Over the years the Lamzin group has published more than 30 papers in Acta Cryst D.


ARP/wARP 7.3 corelease with CCP4 6.3.0

Release 6.3.0 marks a milestone in collaboration between CCP4 and ARP/wARP teams by releasing ARP/wARP Model Building software v7.3 jointly with CCP4 Software Suite. In order to get ARP/wARP Software, academic users need only to select the appropriate package from download pages or with the new CCP4 Package Manager, and type in their name and e-mail address where required. Commerical users will be required also to provide their reference number, obtainable separately from EMBL-EM.

The CCP4 software suite is the world's most comprehensive collection of crystallographic software and for the first time advances of ARP/wARP, developed at the EMBL Hamburg, was fully packaged into a user-friendly bundle with CCP4. Although ARP/wARP has always been compatible with the CCP4 software, data model and style, the need to download and install two separate packages has been a hurdle for novice users. Now, both packages are available together with a single mouse click. This joint release is an acknowledgment of the hard work invested by the research team at EMBL Hamburg, and recognition of ARP/wARP as one of the leading software solutions for building of macromolecular structures.

ARP/wARP 7.3 includes the following major updates and changes:

  • The protocols for the use of NCS in protein chain tracing have been improved and expanded to a wider range of resolutions.
  • Common ligands can now be automatically identified and fit into a specified electron density.
  • The algorithm for modelling partial ligands (cocktail screening) has been replaced with a new one that applies a number of sophisticated numerical features
  • The ARP/wARP graphics front-end, ArpNavigator, automatically assigns secondary structure and has an improved visual presentation of a static model or real time protein or ligand building.
  • Supported computer platforms are Mac powerpc, Mac Intel and Linux (including 32 and 64-bit versions).
  • The ARP/wARP installer has been considerably updated on all platforms.
  • Joint software release and authentication with the CCP4 is now possible.
  • CCP4 6.3.0 and Refmac 5.7.0029 are the recommended versions to use with ARP/wARP 7.3.


The dream of an integrated Biology Infrastructure Life Science Facility at the European XFEL project in Hamburg is one step closer to realisation.

EMBL etcetera on XBI: Victor Larnzin, deputy head of EMBL Hamburg, is coordinating a project to construct, commission, and operate a Biology infrastructure Life Science Center (XBI) at the European XFEL project. [...] The nature of modern structural biology experiments and the fragility and short life span of many samples, mean the ability to prepare, analyse, and interpret experiments in immediate proximity to the XFEL instruments is essential. The project will develop a dedicated infrastructure to support this.

The XBI project was recommended for implementation at the XFEL Council meeting in June and follows the signing of a Memorandum of Understanding by EMBL and XFEL in September 2011 as a basis for future collaborations.[...] "The underlying international and inter-institutional activities will make XBI the world's premier centre in XFEL biological imaging" Victor adds.
Read more


New group member!

Thomas Margraf has joined our group as an EIPOD-Postdoc. Thomas is affiliated as well to our group as to John Briggs group in Heidelberg. Welcome Thomas!


New paper out by Langer GG, Evrard GX, Carolan CG, Lamzin VS.

Fragmentation-tree density representation for crystallographic modelling of bound ligands.
Langer GG, Evrard GX, Carolan CG, Lamzin VS
The identification and modelling of ligands into macromolecular models is important for understanding molecule's function and for designing inhibitors to modulate its activities. We describe new algorithms for the automated building of ligands into electron density maps in crystal structure determination. Location of the ligand-binding site is achieved by matching numerical shape features describing the ligand to those of density clusters using a "fragmentation-tree" density representation. The ligand molecule is built using two distinct algorithms exploiting free atoms with inter-atomic connectivity and Metropolis-based optimisation of the conformational state of the ligand, producing an ensemble of structures from which the final model is derived. The method was validated on several thousand entries from the Protein Data Bank. In the majority of cases, the ligand-binding site could be correctly located and the ligand model built with a coordinate accuracy of better than 1 A. We anticipate that the method will be of routine use to anyone modelling ligands, lead compounds or even compound fragments as part of protein functional analyses or drug design efforts.
J Mol Biol. 2012 Jun 8;419(3-4):211-22. doi: 10.1016/j.jmb.2012.03.012. Epub 2012 Mar 23.   PUBMED


New paper out by Wiegels T, Lamzin VS.

Use of noncrystallographic symmetry for automated model building at medium to low resolution.
Wiegels T, Lamzin VS
A novel method is presented for the automatic detection of noncrystallographic symmetry (NCS) in macromolecular crystal structure determination which does not require the derivation of molecular masks or the segmentation of density. It was found that throughout structure determination the NCS-related parts may be differently pronounced in the electron density. This often results in the modelling of molecular fragments of variable length and accuracy, especially during automated model-building procedures. These fragments were used to identify NCS relations in order to aid automated model building and refinement. In a number of test cases higher completeness and greater accuracy of the obtained structures were achieved, specifically at a crystallographic resolution of 2.3 A or poorer. In the best case, the method allowed the building of up to 15% more residues automatically and a tripling of the average length of the built fragments.
Acta Crystallogr D Biol Crystallogr. 2012 Apr;68(Pt 4):446-53. doi: 10.1107/S0907444911050712. Epub 2012 Mar 16.   PUBMED


New paper out by Wrenger C, MЭller IB, Silber AM, Jordanova R, Lamzin VS, Groves MR.

Aspartate aminotransferase: bridging carbohydrate and energy metabolism in Plasmodium falciparum.
Wrenger C, Muller IB, Silber AM, Jordanova R, Lamzin VS, Groves MR
In this mini-review we briefly examine and summarize evidence on the role of the plasmodial aspartate aminotransferase (AspAT) of the malarial parasite. Recent data have provided information on the products of the purine salvage pathway as well as the glycolytic and oxidative phosphorylation pathways, suggesting that the reaction catalyzed by AspAT is an essential step in all these biochemical processes. While the biological role of the oxidative phosphorylation cycle still remains to be demonstrated, the presence of a single protein that is functional in multiple pathways (i.e. amino acid/purine/pyrimidine biosynthesis and carbohydrate metabolism) provides a high potential for the development of novel strategies to combat the spread of multi-drug resistant malaria.
Curr Drug Metab. 2012 Mar;13(3):332-6.   PUBMED


ARP/wARP around the world

Upcoming ARP/wARP tutorials at CCP4 School on advanced X-ray crystal structure analysis in Melbourne (Australia) in Feb 2012, at the Course for computational methods for macromolecular phasing and refinement in Zaragoza (Spain) in March 2012, and at the 5th annual CCP4 USA Crystallography School at the Advanced Photon Source (APS) synchrotron near Chicago in June 2012


Questionnaire on Biology infrastructure at the XFEL

The European Molecular Biology Laboratory (EMBL) and the European X-ray Free Electron Laser (XFEL) at DESY, Hamburg, Germany, have a keen interest in the development of FEL-based applications in structural biology. Within this framework the EMBL, together with international collaborators from Russia, Sweden and Germany, propose to construct a biology infrastructure at the XFEL facility (expected completion in 2016) to enable biological experiments using the high brilliance, ultrashort pulse duration and high repetition rate coherent X-ray radiation.
The proposed biological sample infrastructure facility will provide:
- support to the international life-science community in generation and handling of challenging samples in immediate proximity to XFEL instruments.
- appropriate selection, quality control and evaluation of samples, including correlative imaging, immediately prior to XFEL experiments.
- standardized technology for data interpretation, including computation and validation of structural models.
In order to ensure efficient operation of the facility and provide optimal services for the international biological community we seek your input to identify the requirements necessary to support these novel biological imaging experiments. We would appreciate your input in the web-based questionnaire available at The results of this survey will be used to identify the most pressing needs that should be taken into account during planning and construction of the infrastructure. We thank you in advance for your cooperation.


ARP/wARP 7.2

We are happy to announce the release of ARP/wARP version 7.2. Please visit for details, software download or remote submission of protein model building.

The major implementations and improvements are:

* The functionality of the graphics front-end, Arp Navigator, has been considerably extended.

* Auto-NCS detection coupled with enhanced protein chain tracing helps obtain more complete models, particularly at resolution lower than 2.5 Å.

* Automated ligand building can screen a cocktail of candidates and has an option to model bound ligands that are partially ordered.

* Supported computer platforms are Mac powerpc, Mac Intel and Linux (including 32 and 64-bit versions).

* The ARP/wARP installer has been updated on all platforms so that its use should be simpler for the users. Users of Mac OSX Intel can also download and install a native application packaged in a DMG file.

* There should be full compatibility of ARP/wARP 7.2 with with CCP4 6.1.13 and Refmac 5.5.0109.


Meet us at the IUCr2011 in Madrid (22-30 August 2011)

We will be at the IUCr in Madrid. There will be four presentations by the Lamzin Group:

Philipp Heuser Pattern recognition for modelling in very low resolution density maps (MS02 Tue 23/08/ 10:15-12:50)

Tim Wiegels Release 7.2 of ARP/wARP Software Suite (Talk in MS58, Sa 27/08/ 10:15-12:50)
Towards more complete models in macromolecular crystal structure determination (Poster, abstract No. 909 in MS 58)

Tutorial @ Crystallographic Software Fayre ARP/wARP for building models of proteins and their binding partners (Fri 26/08/, 16:15-17:00)


New paper out by Unge J, Mueller-Dieckmann C, Panjikar S, Tucker PA, Lamzin VS, Weiss MS.

On the routine use of soft X-rays in macromolecular crystallography. Part V. Molecular replacement and anomalous scattering.
Unge J, Mueller-Dieckmann C, Panjikar S, Tucker PA, Lamzin VS, Weiss MS
Currently, about two thirds of all new macromolecular structures are determined by molecular replacement. In general the method works reliably, but it reaches its limits when the search model differs too much from the target structure in terms of coordinate deviations or completeness. Since anomalously scattering substructures are better conserved than the overall structure, these substructures and the corresponding anomalous intensity differences can be utilized to enhance the performance of molecular-replacement approaches. It is demonstrated that the combined and concomitant use of structure-factor amplitudes and anomalous differences constitutes a promising approach to push the limits of molecular replacement and to make more structures amenable to structure solution by this technique.
Acta Crystallogr D Biol Crystallogr. 2011 Aug;67(Pt 8):729-38. doi: 10.1107/S0907444911024887. Epub 2011 Jul 12.   PUBMED


New Internet Page for the Lamzin Group

We hope you do like our new webpage released today


New group member!

Saul Hazeldine has joined our group as a Scientific Programmer, continuing the work of Gerrit Langer on the development of the Arp Navigator, and the maintenance of the ARP/wARP code and its release! Welcome Saul!


New paper out by Schmidt A, Teeter M, Weckert E and Lamzin VS

Crystal structure of small protein crambin at 0.48 A resolution.
Schmidt A, Teeter M, Weckert E, Lamzin VS
With the development of highly brilliant and extremely intense synchrotron X-ray sources, extreme high-resolution limits for biological samples are now becoming attainable. Here, a study is presented that sets the record in crystallographic resolution for a biological macromolecule. The structure of the small protein crambin was determined to 0.48 A resolution on the PETRA II ring before its conversion to a dedicated synchrotron-radiation source. The results reveal a wealth of details in electron density and demonstrate the possibilities that are potentially offered by a high-energy source. The question now arises as to what the true limits are in terms of what can be seen at such high resolution. From what can be extrapolated from the results using crystals of crambin, this limit would be at approximately 0.40 A, which approaches that for smaller compounds.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Apr 1;67(Pt 4):424-8. doi: 10.1107/S1744309110052607. Epub 2011 Mar 24.   PUBMED


New publication by J. Hattne and V.S. Lamzin

A moment invariant for evaluating the chirality of three-dimensional objects.
Hattne J, Lamzin VS
Chirality is an important feature of three-dimensional objects and a key concept in chemistry, biology and many other disciplines. However, it has been difficult to quantify, largely owing to computational complications. Here we present a general chirality measure, called the chiral invariant (CI), which is applicable to any three-dimensional object containing a large amount of data. The CI distinguishes the hand of the object and quantifies the degree of its handedness. It is invariant to the translation, rotation and scale of the object, and tolerant to a modest amount of noise in the experimental data. The invariant is expressed in terms of moments and can be computed in almost no time. Because of its universality and computational efficiency, the CI is suitable for a wide range of pattern-recognition problems. We demonstrate its applicability to molecular atomic models and their electron density maps. We show that the occurrence of the conformations of the macromolecular polypeptide backbone is related to the value of the CI of the constituting peptide fragments. We also illustrate how the CI can be used to assess the quality of a crystallographic electron density map.
J R Soc Interface. 2011 Jan 6;8(54):144-51. doi: 10.1098/rsif.2010.0297. Epub 2010 Aug 4.   PUBMED


New publication by D.Watts, J. MЭller-Dieckmann, G. Tsakanova, V.S. Lamzin and M.R. Groves

Quantitive evaluation of macromolecular crystallization experiments using 1,8-ANS fluorescence.
Watts D, Muller-Dieckmann J, Tsakanova G, Lamzin VS, Groves MR
Modern X-ray structure analysis and advances in high-throughput robotics have allowed a significant increase in the number of conditions screened for a given sample volume. An efficient evaluation of the increased amount of crystallization trials in order to identify successful experiments is now urgently required. A novel approach is presented for the visualization of crystallization experiments using fluorescence from trace amounts of a nonspecific dye. The fluorescence images obtained strongly contrast protein crystals against other phenomena, such as precipitation and phase separation. Novel software has been developed to quantitatively evaluate the crystallization outcome based on a biophysical metric correlated with voxel protein concentration. In >1500 trials, 85.6% of the successful crystallization experiments were correctly identified, yielding a 50% reduction in the number of 'missed hits' compared with current automated approaches. The use of the method in the crystallization of three previously uncharacterized proteins from the malarial parasite Plasmodium falciparum is further demonstrated.
Acta Crystallogr D Biol Crystallogr. 2010 Aug;66(Pt 8):901-8. doi: 10.1107/S0907444910020664. Epub 2010 Jul 10.   PUBMED


New publication by A.Schmidt and V.S. Lamzin

Internal motion in protein crystal structures.
Schmidt A, Lamzin VS
The binding states of the substrates and the environment have significant influence on protein motion. We present the analysis of such motion derived from anisotropic atomic displacement parameters (ADPs) in a set of atomic resolution protein structures. Local structural motion caused by ligand binding as well as functional loops showing cooperative patterns of motion could be inferred. The results are in line with proposed protonation states, hydrogen bonding patterns and the location of distinctly flexible regions: we could locate the mobile active site loop in a virus integrase, distinguish the subdomains in RNAse A and hydroxynitrile lyase, and reconstruct the molecular architecture in a xylanase. We demonstrate that the ADP-based motion analysis provides information at high level of detail and that the structural changes needed for substrate attachment or release may be derived from single X-ray structures.
Protein Sci. 2010 May;19(5):944-53. doi: 10.1002/pro.371.   PUBMED


ARP/wARP 7.1 released

We are happy to announce the release of ARP/wARP version 7.1.
Please visit for details and software download.
The major implementations and improvements are:
  • A prototype of the molecular graphics ARP/wARP front-end, allowing the display of molecules and electron densities.
  • A prototype version of the new module for building poly-nucleotides (DNA or RNA).
  • Improved and faster protein chain tracing with higher performance at lower resolution.
  • The loop building as well as helix/strand building are now also inherent parts of protein model building, resulting in enhanced model completeness.
  • Refinement procedures during automated model building have been enhanced in the new versions of our preferred refinement engine, REFMAC, notably including the implementation of 'conditional restraints'.
  • Direct use of experimental single-wavelength anomalous diffraction data (SAD) during model building is now also possible.
  • Improved performance of automated ligand building.
  • Supported computer platforms are Mac powerpc, Mac Intel and Linux (including 32 and 64-bit versions and itanium).

Merry Xmas and Happy New Year!

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