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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Moriarty, NW; Janowski, PA; Swails, JM; Nguyen, H; Richardson, JS; Case, DA; Adams, PD

Published Date

  • January 1, 2020

Published In

Volume / Issue

  • 76 / Pt 1

Start / End Page

  • 51 - 62

PubMed ID

  • 31909743

Pubmed Central ID

  • 31909743

Electronic International Standard Serial Number (EISSN)

  • 2059-7983

Digital Object Identifier (DOI)

  • 10.1107/S2059798319015134

Language

  • eng

Conference Location

  • United States