Phaser.MRage: Automated Molecular Replacement

Overview

Journal Acta Crystallogr D Biol Crystallogr

Specialty Chemistry

Date 2013 Nov 6

PMID 24189240

Citations 139

Authors

Gabor Bunkoczi

Nathaniel Echols

Airlie J McCoy

Robert D Oeffner

Paul D Adams

Randy J Read

Affiliations

Soon will be listed here.

Abstract

Phaser.MRage is a molecular-replacement automation framework that implements a full model-generation workflow and provides several layers of model exploration to the user. It is designed to handle a large number of models and can distribute calculations efficiently onto parallel hardware. In addition, phaser.MRage can identify correct solutions and use this information to accelerate the search. Firstly, it can quickly score all alternative models of a component once a correct solution has been found. Secondly, it can perform extensive analysis of identified solutions to find protein assemblies and can employ assembled models for subsequent searches. Thirdly, it is able to use a priori assembly information (derived from, for example, homologues) to speculatively place and score molecules, thereby customizing the search procedure to a certain class of protein molecule (for example, antibodies) and incorporating additional biological information into molecular replacement.

Citing Articles

Broadly neutralizing antibodies isolated from HEV convalescents confer protective effects in human liver-chimeric mice.

Ssebyatika G, Dinkelborg K, Stroh L, Hinte F, Corneillie L, Hueffner L Nat Commun. 2025; 16(1):1995.

PMID: 40011441 PMC: 11865592. DOI: 10.1038/s41467-025-57182-1.

Designing small molecules that target a cryptic RNA binding site via base displacement.

Batey R, Olenginski L, Wierzba A, Laursen S Res Sq. 2025; .

PMID: 39975918 PMC: 11838749. DOI: 10.21203/rs.3.rs-5836924/v1.

NADH-bound AIF activates the mitochondrial CHCHD4/MIA40 chaperone by a substrate-mimicry mechanism.

Brosey C, Shen R, Tainer J EMBO J. 2025; 44(4):1220-1248.

PMID: 39806100 PMC: 11832770. DOI: 10.1038/s44318-024-00360-6.

Genetic and biochemical characterization of a radical SAM enzyme required for post-translational glutamine methylation of methyl-coenzyme M reductase.

Rodriguez Carrero R, Lloyd C, Borkar J, Nath S, Mirica L, Nair S mBio. 2025; 16(2):e0354624.

PMID: 39772843 PMC: 11796369. DOI: 10.1128/mbio.03546-24.

Affinity Tag-Free Purification of SARS-CoV-2 N Protein and Its Crystal Structure in Complex with ssDNA.

Maiti A, Matsuo H Biomolecules. 2025; 14(12.

PMID: 39766245 PMC: 11673995. DOI: 10.3390/biom14121538.

References

LARKIN M, Blackshields G, Brown N, Chenna R, McGettigan P, McWilliam H . Clustal W and Clustal X version 2.0. Bioinformatics. 2007; 23(21):2947-8. DOI: 10.1093/bioinformatics/btm404. View

Ling H, Boodhoo A, Hazes B, Cummings M, Armstrong G, Brunton J . Structure of the shiga-like toxin I B-pentamer complexed with an analogue of its receptor Gb3. Biochemistry. 1998; 37(7):1777-88. DOI: 10.1021/bi971806n. View

Stokes-Rees I, Sliz P . Protein structure determination by exhaustive search of Protein Data Bank derived databases. Proc Natl Acad Sci U S A. 2010; 107(50):21476-81. PMC: 3003117. DOI: 10.1073/pnas.1012095107. View

Soding J, Biegert A, Lupas A . The HHpred interactive server for protein homology detection and structure prediction. Nucleic Acids Res. 2005; 33(Web Server issue):W244-8. PMC: 1160169. DOI: 10.1093/nar/gki408. View

Piao S, Song Y, Kim J, Park S, Park J, Lee B . Crystal structure of a clip-domain serine protease and functional roles of the clip domains. EMBO J. 2005; 24(24):4404-14. PMC: 1356332. DOI: 10.1038/sj.emboj.7600891. View

Terwilliger T, Grosse-Kunstleve R, Afonine P, Moriarty N, Zwart P, Hung L . Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard. Acta Crystallogr D Biol Crystallogr. 2007; 64(Pt 1):61-9. PMC: 2394820. DOI: 10.1107/S090744490705024X. View

Chothia C, Lesk A . The relation between the divergence of sequence and structure in proteins. EMBO J. 1986; 5(4):823-6. PMC: 1166865. DOI: 10.1002/j.1460-2075.1986.tb04288.x. View

McNicholas S, Potterton E, Wilson K, Noble M . Presenting your structures: the CCP4mg molecular-graphics software. Acta Crystallogr D Biol Crystallogr. 2011; 67(Pt 4):386-94. PMC: 3069754. DOI: 10.1107/S0907444911007281. View

Leiros H, McSweeney S, Smalas A . Atomic resolution structures of trypsin provide insight into structural radiation damage. Acta Crystallogr D Biol Crystallogr. 2001; 57(Pt 4):488-97. DOI: 10.1107/s0907444901000646. View

10.

Long F, Vagin A, Young P, Murshudov G . BALBES: a molecular-replacement pipeline. Acta Crystallogr D Biol Crystallogr. 2007; 64(Pt 1):125-32. PMC: 2394813. DOI: 10.1107/S0907444907050172. View

11.

Sakai H, Vassylyeva M, Matsuura T, Sekine S, Gotoh K, Nishiyama M . Crystal structure of a lysine biosynthesis enzyme, LysX, from Thermus thermophilus HB8. J Mol Biol. 2003; 332(3):729-40. DOI: 10.1016/s0022-2836(03)00946-x. View

12.

Altschul S, Madden T, Schaffer A, Zhang J, Zhang Z, Miller W . Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997; 25(17):3389-402. PMC: 146917. DOI: 10.1093/nar/25.17.3389. View

13.

McCoy A, Grosse-Kunstleve R, Adams P, Winn M, Storoni L, Read R . Phaser crystallographic software. J Appl Crystallogr. 2009; 40(Pt 4):658-674. PMC: 2483472. DOI: 10.1107/S0021889807021206. View

14.

Jaroszewski L, Rychlewski L, Li Z, Li W, Godzik A . FFAS03: a server for profile--profile sequence alignments. Nucleic Acids Res. 2005; 33(Web Server issue):W284-8. PMC: 1160179. DOI: 10.1093/nar/gki418. View

15.

McCoy A, Grosse-Kunstleve R, Storoni L, Read R . Likelihood-enhanced fast translation functions. Acta Crystallogr D Biol Crystallogr. 2005; 61(Pt 4):458-64. DOI: 10.1107/S0907444905001617. View

16.

Vagin A, Teplyakov A . Molecular replacement with MOLREP. Acta Crystallogr D Biol Crystallogr. 2010; 66(Pt 1):22-5. DOI: 10.1107/S0907444909042589. View

17.

Krissinel E, Henrick K . Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions. Acta Crystallogr D Biol Crystallogr. 2004; 60(Pt 12 Pt 1):2256-68. DOI: 10.1107/S0907444904026460. View

18.

Keegan R, Long F, Fazio V, Winn M, Murshudov G, Vagin A . Evaluating the solution from MrBUMP and BALBES. Acta Crystallogr D Biol Crystallogr. 2011; 67(Pt 4):313-23. PMC: 3069746. DOI: 10.1107/S0907444911007530. View

19.

Berman H, Henrick K, Nakamura H . Announcing the worldwide Protein Data Bank. Nat Struct Biol. 2003; 10(12):980. DOI: 10.1038/nsb1203-980. View

20.

Stein P, Boodhoo A, Tyrrell G, Brunton J, Read R . Crystal structure of the cell-binding B oligomer of verotoxin-1 from E. coli. Nature. 1992; 355(6362):748-50. DOI: 10.1038/355748a0. View