Janowski, Pawel, Moriarty, Nigel, Kelley, Brian, Case, David, York, Darrin, Adams, Paul and Warren, Greg (2016) IMPROVED LIGAND GEOMETRIES IN CRYSTALLOGRAPHIC REFINEMENT USING AFITT IN PHENIX. Acta Crystallographica Section D, 72 (9). pp. 1062-1072. ISSN 2059-7983

Abstract

Modern crystal refinement programs rely on geometry restraints to overcome the challenge of a low data to parameter ratio. While the classical Engh & Huber restraints work well for standard residues, the chemical complexity of ligands and small molecules presents a particular challenge. Most current approaches either limit ligand restraints to those that can be readily described in the Crystallographic Information File format, thus sacrificing chemical flexibility and energetic accuracy, or they employ protocols that lengthen refinement times and hinder automated refinement workflows. We present the results of combining AFITT and the Phenix software suite, which together generate more chemically accurate models for small molecules. A Phenix-AFITT refinement uses a full molecular mechanics force field for ligands during refinement. It is fully integrated with a standard refinement protocol and requires practically no additional steps from the user, thus making it ideal for high throughput workflows. Phenix-AFITT refinements also handle multiple ligands in a single model, alternate conformations and covalently bound ligands. Refinements using AFITT significantly reduce ligand energies and lead to improved geometries without detriment to R-free factors.

Item Type:	Article
Keywords:	X-ray crystallography; PHENIX ;ligand strain; high-throughput crystallography
Date Deposited:	11 Oct 2016 00:45
Last Modified:	11 Oct 2016 00:45
URI:	https://oak.novartis.com/id/eprint/26036