Polarizable atomic multipole X-ray refinement: weighting schemes for macromolecular diffraction

T D Fenn; M J Schnieders

doi:10.1107/S0907444911039060

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$Polarizable atomic multipole X-ray refinement: weighting schemes for macromolecular diffraction$

Journal article

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Polarizable atomic multipole X-ray refinement: weighting schemes for macromolecular diffraction

T D Fenn and M J Schnieders

Acta crystallographica. Section D, Biological crystallography, Vol.67(Pt 11), pp.957-965

11/2011

DOI: 10.1107/S0907444911039060

PMID: 22101822

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Abstract

In the past, weighting between the sum of chemical and data-based targets in macromolecular crystallographic refinement was based on comparing the gradients or Hessian diagonal terms of the two potential functions. Here, limitations of this scheme are demonstrated, especially in the context of a maximum-likelihood target that is inherently weighted by the model and data errors. In fact, the congruence between the maximum-likelihood target and a chemical potential based on polarizable atomic multipole electrostatics evaluated with Ewald summation has opened the door to a transferable static weight. An optimal static weight is derived from first principles and is demonstrated to be transferable across a broad range of data resolutions in the context of a recent implementation of X-ray crystallographic refinement using the polarizable AMOEBA force field and it is shown that the resulting models are balanced with respect to optimizing both R(free) and MolProbity scores. Conversely, the classical automatic weighting scheme is shown to lead to underfitting or overfitting of the data and poor model geometry. The benefits of this approach for low-resolution diffraction data, where the need for prior chemical information is of particular importance, are also highlighted. It is demonstrated that this method is transferable between low- and high-resolution maximum-likelihood-based crystallographic refinement, which proves for the first time that resolution-dependent parameterization of either the weight or the chemical potential is unnecessary.

Models, Theoretical

Molecular Weight

Models, Chemical

Humans

Computational Biology

Crystallization

Crystallography, X-Ray

Likelihood Functions

Animals

Macromolecular Substances - chemistry

X-Ray Diffraction

Protein Conformation

Software

Proteins - chemistry

Details

Title: Subtitle: Polarizable atomic multipole X-ray refinement: weighting schemes for macromolecular diffraction
Creators: T D Fenn - Department of Bioengineering, Stanford University, Stanford, California, USA. fenn@stanford.edu
M J Schnieders
Resource Type: Journal article
Publication Details: Acta crystallographica. Section D, Biological crystallography, Vol.67(Pt 11), pp.957-965
DOI: 10.1107/S0907444911039060
PMID: 22101822
NLM abbreviation: Acta Crystallogr D Biol Crystallogr
ISSN: 1399-0047
eISSN: 1399-0047
Publisher: United States
Language: English
Date published: 11/2011
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Biochemistry and Molecular Biology
Record Identifier: 9984024552602771

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