Cargando…

Improved chemistry restraints for crystallographic refinement by integrating the Amber force field into Phenix

The refinement of biomolecular crystallographic models relies on geometric restraints to help to address the paucity of experimental data typical in these experiments. Limitations in these restraints can degrade the quality of the resulting atomic models. Here, an integration of the full all-atom Am...

Descripción completa

Detalles Bibliográficos
Autores principales: Moriarty, Nigel W., Janowski, Pawel A., Swails, Jason M., Nguyen, Hai, Richardson, Jane S., Case, David A., Adams, Paul D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Union of Crystallography 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939439/
https://www.ncbi.nlm.nih.gov/pubmed/31909743
http://dx.doi.org/10.1107/S2059798319015134
_version_ 1783484211932430336
author Moriarty, Nigel W.
Janowski, Pawel A.
Swails, Jason M.
Nguyen, Hai
Richardson, Jane S.
Case, David A.
Adams, Paul D.
author_facet Moriarty, Nigel W.
Janowski, Pawel A.
Swails, Jason M.
Nguyen, Hai
Richardson, Jane S.
Case, David A.
Adams, Paul D.
author_sort Moriarty, Nigel W.
collection PubMed
description The refinement of biomolecular crystallographic models relies on geometric restraints to help to address the paucity of experimental data typical in these experiments. Limitations in these restraints can degrade the quality of the resulting atomic models. Here, an integration of the full all-atom Amber molecular-dynamics force field into Phenix crystallographic refinement is presented, which enables more complete modeling of biomolecular chemistry. The advantages of the force field include a carefully derived set of torsion-angle potentials, an extensive and flexible set of atom types, Lennard–Jones treatment of nonbonded interactions and a full treatment of crystalline electrostatics. The new combined method was tested against conventional geometry restraints for over 22 000 protein structures. Structures refined with the new method show substantially improved model quality. On average, Ramachandran and rotamer scores are somewhat better, clashscores and MolProbity scores are significantly improved, and the modeling of electrostatics leads to structures that exhibit more, and more correct, hydrogen bonds than those refined using traditional geometry restraints. In general it is found that model improvements are greatest at lower resolutions, prompting plans to add the Amber target function to real-space refinement for use in electron cryo-microscopy. This work opens the door to the future development of more advanced applications such as Amber-based ensemble refinement, quantum-mechanical representation of active sites and improved geometric restraints for simulated annealing.
format Online
Article
Text
id pubmed-6939439
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher International Union of Crystallography
record_format MEDLINE/PubMed
spelling pubmed-69394392020-01-06 Improved chemistry restraints for crystallographic refinement by integrating the Amber force field into Phenix Moriarty, Nigel W. Janowski, Pawel A. Swails, Jason M. Nguyen, Hai Richardson, Jane S. Case, David A. Adams, Paul D. Acta Crystallogr D Struct Biol Research Papers The refinement of biomolecular crystallographic models relies on geometric restraints to help to address the paucity of experimental data typical in these experiments. Limitations in these restraints can degrade the quality of the resulting atomic models. Here, an integration of the full all-atom Amber molecular-dynamics force field into Phenix crystallographic refinement is presented, which enables more complete modeling of biomolecular chemistry. The advantages of the force field include a carefully derived set of torsion-angle potentials, an extensive and flexible set of atom types, Lennard–Jones treatment of nonbonded interactions and a full treatment of crystalline electrostatics. The new combined method was tested against conventional geometry restraints for over 22 000 protein structures. Structures refined with the new method show substantially improved model quality. On average, Ramachandran and rotamer scores are somewhat better, clashscores and MolProbity scores are significantly improved, and the modeling of electrostatics leads to structures that exhibit more, and more correct, hydrogen bonds than those refined using traditional geometry restraints. In general it is found that model improvements are greatest at lower resolutions, prompting plans to add the Amber target function to real-space refinement for use in electron cryo-microscopy. This work opens the door to the future development of more advanced applications such as Amber-based ensemble refinement, quantum-mechanical representation of active sites and improved geometric restraints for simulated annealing. International Union of Crystallography 2020-01-01 /pmc/articles/PMC6939439/ /pubmed/31909743 http://dx.doi.org/10.1107/S2059798319015134 Text en © Moriarty et al. 2020 http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.http://creativecommons.org/licenses/by/4.0/
spellingShingle Research Papers
Moriarty, Nigel W.
Janowski, Pawel A.
Swails, Jason M.
Nguyen, Hai
Richardson, Jane S.
Case, David A.
Adams, Paul D.
Improved chemistry restraints for crystallographic refinement by integrating the Amber force field into Phenix
title Improved chemistry restraints for crystallographic refinement by integrating the Amber force field into Phenix
title_full Improved chemistry restraints for crystallographic refinement by integrating the Amber force field into Phenix
title_fullStr Improved chemistry restraints for crystallographic refinement by integrating the Amber force field into Phenix
title_full_unstemmed Improved chemistry restraints for crystallographic refinement by integrating the Amber force field into Phenix
title_short Improved chemistry restraints for crystallographic refinement by integrating the Amber force field into Phenix
title_sort improved chemistry restraints for crystallographic refinement by integrating the amber force field into phenix
topic Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939439/
https://www.ncbi.nlm.nih.gov/pubmed/31909743
http://dx.doi.org/10.1107/S2059798319015134
work_keys_str_mv AT moriartynigelw improvedchemistryrestraintsforcrystallographicrefinementbyintegratingtheamberforcefieldintophenix
AT janowskipawela improvedchemistryrestraintsforcrystallographicrefinementbyintegratingtheamberforcefieldintophenix
AT swailsjasonm improvedchemistryrestraintsforcrystallographicrefinementbyintegratingtheamberforcefieldintophenix
AT nguyenhai improvedchemistryrestraintsforcrystallographicrefinementbyintegratingtheamberforcefieldintophenix
AT richardsonjanes improvedchemistryrestraintsforcrystallographicrefinementbyintegratingtheamberforcefieldintophenix
AT casedavida improvedchemistryrestraintsforcrystallographicrefinementbyintegratingtheamberforcefieldintophenix
AT adamspauld improvedchemistryrestraintsforcrystallographicrefinementbyintegratingtheamberforcefieldintophenix