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.

doi:10.1101/724567

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

Journal Article · Wed Aug 07 00:00:00 EDT 2019 · Acta Crystallographica. Section D: Biological Crystallography

DOI:https://doi.org/10.1101/724567· OSTI ID:1735534

^[1]; Janowski, Pawel A. ^[2]; Swails, Jason M. ^[2]; Nguyen, Hai ^[2]; Richardson, Jane S. ^[3]; Case, David A. ^[1]; Adams, Paul D. ^[4]

Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Rutgers Univ., Piscataway, NJ (United States)
Duke Univ., Durham, NC (United States)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States)

The refinement of biomolecular crystallographic models relies on geometric restraints to help address the paucity of experimental data typical in these experiments. Limitations in these restraints can degrade the quality of the resulting atomic models. Here we present an integration of the full all-atom Amber molecular dynamics force field into Phenix crystallographic refinement, which enables a 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 non-bonded interactions and a full treatment of crystalline electrostatics. The new combined method was tested against conventional geometry restraints for over twenty-two thousand protein structures. Structures refined with the new method show substantially improved model quality. On average, Ramachandran and rotamer scores are somewhat better; clash scores and MolProbity scores are significantly improved; and the modelling of electrostatics leads to structures that exhibit more, and more correct, hydrogen bonds than those refined with traditional geometry restraints. We find in general 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. This document contains embedded data - to preserve data integrity, please ensure where possible that the IUCr Word tools (available from http://journals.iucr.org/services/docxtemplate/) are installed when editing this document. The full Amber force field has been integrated into Phenix as an alternative refinement target. With a slight loss in speed, it achieves improved stereochemistry, fewer steric clashes and better hydrogen bonds.

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Research Organization:: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1735534

Journal Information:: Acta Crystallographica. Section D: Biological Crystallography, Vol. 1; ISSN 0907-4449

Publisher:: International Union of CrystallographyCopyright Statement

Country of Publication:: United States

Language:: English

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