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Title: Exploring the speed and performance of molecular replacement with AMPLE using QUARK ab initio protein models

Abstract

Two ab initio modelling programs solve complementary sets of targets, enhancing the success of AMPLE with small proteins. AMPLE clusters and truncates ab initio protein structure predictions, producing search models for molecular replacement. Here, an interesting degree of complementarity is shown between targets solved using the different ab initio modelling programs QUARK and ROSETTA. Search models derived from either program collectively solve almost all of the all-helical targets in the test set. Initial solutions produced by Phaser after only 5 min perform surprisingly well, improving the prospects for in situ structure solution by AMPLE during synchrotron visits. Taken together, the results show the potential for AMPLE to run more quickly and successfully solve more targets than previously suspected.

Authors:
 [1]; ;  [2];  [3];  [4];  [2];  [5];  [2];  [6]
  1. STFC Rutherford Appleton Laboratory, Didcot OX11 0FA (United Kingdom)
  2. University of Liverpool, Liverpool L69 7ZB (United Kingdom)
  3. Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037 (United States)
  4. University of Michigan, Ann Arbor, MI 48109 (United States)
  5. Science and Technology Facilities Council Daresbury Laboratory, Warrington WA4 4AD (United Kingdom)
  6. (United Kingdom)
Publication Date:
OSTI Identifier:
22347711
Resource Type:
Journal Article
Resource Relation:
Journal Name: Acta Crystallographica. Section D: Biological Crystallography; Journal Volume: 71; Journal Issue: Pt 2; Other Information: PMCID: PMC4321487; PMID: 25664744; PUBLISHER-ID: rr5080; OAI: oai:pubmedcentral.nih.gov:4321487; Copyright (c) Keegan et al. 2015; This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
Denmark
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; FORECASTING; MATHEMATICAL SOLUTIONS; PERFORMANCE; POTENTIALS; PROTEIN STRUCTURE; PROTEINS; SOLUTIONS; SYNCHROTRONS; VELOCITY

Citation Formats

Keegan, Ronan M., Bibby, Jaclyn, Thomas, Jens, Xu, Dong, Zhang, Yang, Mayans, Olga, Winn, Martyn D., Rigden, Daniel J., E-mail: drigden@liv.ac.uk, and STFC Rutherford Appleton Laboratory, Didcot OX11 0FA. Exploring the speed and performance of molecular replacement with AMPLE using QUARK ab initio protein models. Denmark: N. p., 2015. Web. doi:10.1107/S1399004714025784.
Keegan, Ronan M., Bibby, Jaclyn, Thomas, Jens, Xu, Dong, Zhang, Yang, Mayans, Olga, Winn, Martyn D., Rigden, Daniel J., E-mail: drigden@liv.ac.uk, & STFC Rutherford Appleton Laboratory, Didcot OX11 0FA. Exploring the speed and performance of molecular replacement with AMPLE using QUARK ab initio protein models. Denmark. doi:10.1107/S1399004714025784.
Keegan, Ronan M., Bibby, Jaclyn, Thomas, Jens, Xu, Dong, Zhang, Yang, Mayans, Olga, Winn, Martyn D., Rigden, Daniel J., E-mail: drigden@liv.ac.uk, and STFC Rutherford Appleton Laboratory, Didcot OX11 0FA. 2015. "Exploring the speed and performance of molecular replacement with AMPLE using QUARK ab initio protein models". Denmark. doi:10.1107/S1399004714025784.
@article{osti_22347711,
title = {Exploring the speed and performance of molecular replacement with AMPLE using QUARK ab initio protein models},
author = {Keegan, Ronan M. and Bibby, Jaclyn and Thomas, Jens and Xu, Dong and Zhang, Yang and Mayans, Olga and Winn, Martyn D. and Rigden, Daniel J., E-mail: drigden@liv.ac.uk and STFC Rutherford Appleton Laboratory, Didcot OX11 0FA},
abstractNote = {Two ab initio modelling programs solve complementary sets of targets, enhancing the success of AMPLE with small proteins. AMPLE clusters and truncates ab initio protein structure predictions, producing search models for molecular replacement. Here, an interesting degree of complementarity is shown between targets solved using the different ab initio modelling programs QUARK and ROSETTA. Search models derived from either program collectively solve almost all of the all-helical targets in the test set. Initial solutions produced by Phaser after only 5 min perform surprisingly well, improving the prospects for in situ structure solution by AMPLE during synchrotron visits. Taken together, the results show the potential for AMPLE to run more quickly and successfully solve more targets than previously suspected.},
doi = {10.1107/S1399004714025784},
journal = {Acta Crystallographica. Section D: Biological Crystallography},
number = Pt 2,
volume = 71,
place = {Denmark},
year = 2015,
month = 2
}
  • Processing of NMR structures for molecular replacement by AMPLE works well. AMPLE is a program developed for clustering and truncating ab initio protein structure predictions into search models for molecular replacement. Here, it is shown that its core cluster-and-truncate methods also work well for processing NMR ensembles into search models. Rosetta remodelling helps to extend success to NMR structures bearing low sequence identity or high structural divergence from the target protein. Potential future routes to improved performance are considered and practical, general guidelines on using AMPLE are provided.
  • Cited by 1
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