Campus Units

Biochemistry, Biophysics and Molecular Biology, Roy J. Carver Department of

Document Type

Article

Publication Version

Accepted Manuscript

Publication Date

2-2012

Journal or Book Title

Proteins: Structure, Function, and Bioinformatics

Volume

80

Issue

2

First Page

335

Last Page

341

DOI

10.1002/prot.23240

Abstract

Structural refinement of predicted models of biological macromolecules using atomistic or coarse-grained molecular force fields having various degree of error are investigated. The goal of this analysis is to estimate what is the probability for designing an effective structural refinement based on computations of conformational energies using force field, and starting from a structure predicted from the sequence (using template-based, or template-free modeling), and refining it to bring the structure into closer proximity to the native state. It is widely believed that it should be possible to develop such a successful structure refinement algorithm by applying an iterative procedure with stochastic sampling and appropriate energy function, which assesses the quality (correctness) of protein decoys. Here an analysis of noise in an artificially introduced scoring function is investigated for a model of an ideal sampling scheme, where the underlying distribution of RMSDs is assumed to be Gaussian. Sampling of the conformational space is performed by random generation of RMSD values. We demonstrate that whenever the random noise in a force field exceeds some level, it is impossible to obtain reliable structural refinement. The magnitude of the noise, above which a structural refinement, on average is impossible, depends strongly on the quality of sampling scheme and a size of the protein. Finally, possible strategies to overcome the intrinsic limitations in the force fields for impacting the development of successful refinement algorithms are discussed.

Comments

This is the peer reviewed version of the following article: Gniewek, Pawel, Andrzej Kolinski, Robert L. Jernigan, and Andrzej Kloczkowski. "How noise in force fields can affect the structural refinement of protein models?" Proteins: Structure, Function, and Bioinformatics 80, no. 2 (2012): 335-341, which has been published in final form at DOI: 10.1002/prot.23240. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

Copyright Owner

Wiley Periodicals, Inc.

Language

en

File Format

application/pdf

Download
Published Version

Share

COinS