Polarizable atomic multipole x-ray refinement: hydration geometry and application to macromolecules

Timothy D Fenn; Michael J Schnieders; Axel T Brunger; Vijay S Pande

doi:10.1016/j.bpj.2010.02.057

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Polarizable atomic multipole x-ray refinement: hydration geometry and application to macromolecules

Journal article

Open access

Peer reviewed

Polarizable atomic multipole x-ray refinement: hydration geometry and application to macromolecules

Timothy D Fenn, Michael J Schnieders, Axel T Brunger and Vijay S Pande

Biophysical journal, Vol.98(12), pp.2984-2992

06/16/2010

DOI: 10.1016/j.bpj.2010.02.057

PMCID: PMC2884231

PMID: 20550911

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Abstract

We recently developed a polarizable atomic multipole refinement method assisted by the AMOEBA force field for macromolecular crystallography. Compared to standard refinement procedures, the method uses a more rigorous treatment of x-ray scattering and electrostatics that can significantly improve the resultant information contained in an atomic model. We applied this method to high-resolution lysozyme and trypsin data sets, and validated its utility for precisely describing biomolecular electron density, as indicated by a 0.4-0.6% decrease in the R- and R(free)-values, and a corresponding decrease in the relative energy of 0.4-0.8 Kcal/mol/residue. The re-refinements illustrate the ability of force-field electrostatics to orient water networks and catalytically relevant hydrogens, which can be used to make predictions regarding active site function, activity, and protein-ligand interaction energies. Re-refinement of a DNA crystal structure generates the zigzag spine pattern of hydrogen bonding in the minor groove without manual intervention. The polarizable atomic multipole electrostatics model implemented in the AMOEBA force field is applicable and informative for crystal structures solved at any resolution.

Reproducibility of Results

Muramidase - chemistry

Substrate Specificity

Crystallography, X-Ray

Muramidase - metabolism

Static Electricity

Trypsin - metabolism

Molecular Dynamics Simulation

DNA - chemistry

Animals

Macromolecular Substances - chemistry

Water - chemistry

Protein Conformation

Nucleic Acid Conformation

Trypsin - chemistry

Macromolecular Substances - metabolism

Details

Title: Subtitle: Polarizable atomic multipole x-ray refinement: hydration geometry and application to macromolecules
Creators: Timothy D Fenn - Department of Molecular and Cellular Physiology, Stanford University, Stanford, California, USA
Michael J Schnieders
Axel T Brunger
Vijay S Pande
Resource Type: Journal article
Publication Details: Biophysical journal, Vol.98(12), pp.2984-2992
Publisher: United States
DOI: 10.1016/j.bpj.2010.02.057
PMID: 20550911
PMCID: PMC2884231
ISSN: 0006-3495
eISSN: 1542-0086
Grant note: Howard Hughes Medical Institute U54 GM072970 / NIGMS NIH HHS
Language: English
Date published: 06/16/2010
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Biochemistry and Molecular Biology
Record Identifier: 9984025286002771

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