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.
Copyright Owner
Wiley Periodicals, Inc.
Copyright Date
2011
Language
en
File Format
application/pdf
Recommended Citation
Gniewek, Pawel; Kolinski, Andrzej; Jernigan, Robert L.; and Kloczkowski, Andrzej, "How noise in force fields can affect the structural refinement of protein models" (2012). Biochemistry, Biophysics and Molecular Biology Publications. 145.
https://lib.dr.iastate.edu/bbmb_ag_pubs/145
Included in
Biochemistry Commons, Biophysics Commons, Molecular Biology Commons, Structural Biology Commons
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.