Can molecular dynamics simulations provide high-resolution refinement of protein structure?

Can molecular dynamics simulations provide high-resolution refinement of protein structure? Research Abstract Details 

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Can molecular dynamics simulations provide high-resolution refinement of protein structure? Abstract Text:

Jianhan Chen,Charles L Brooks,

Recent advances in efficient and accurate treatment of solvent with the generalized Born approximation (GB) have made it possible to substantially refine the protein structures generated by various prediction tools through detailed molecular dynamics simulations. As demonstrated in a recent CASPR experiment, improvement can be quite reliably achieved when the initial models are sufficiently close to the native basin (e.g., 3-4 A C(alpha) RMSD). A key element to effective refinement is to incorporate reliable structural information into the simulation protocol. Without intimate knowledge of the target and prediction protocol used to generate the initial structural models, it can be assumed that the regular secondary structure elements (helices and strands) and overall fold topology are largely correct to start with, such that the protocol limits itself to the scope of refinement and focuses the sampling in vicinity of the initial structure. The secondary structures can be enforced by dihedral restraints and the topology through structural contacts, implemented as either multiple pair-wise C(alpha) distance restraints or a single sidechain distance matrix restraint. The restraints are weakly imposed with flat-bottom potentials to allow sufficient flexibility for structural rearrangement. Refinement is further facilitated by enhanced sampling of advanced techniques such as the replica exchange method (REX). In general, for single domain proteins of small to medium sizes, 3-5 nanoseconds of REX/GB refinement simulations appear to be sufficient for reasonable convergence. Clustering of the resulting structural ensembles can yield refined models over 1.0 A closer to the native structure in C(alpha) RMSD. Substantial improvement of sidechain contacts and rotamer states can also be achieved in most cases. Additional improvement is possible with longer sampling and knowledge of the robust structural features in the initial models for a given prediction protocol. Nevertheless, limitations still exist in sampling as well as force field accuracy, manifested as difficulty in refinement of long and flexible loops.

Can molecular dynamics simulations provide high-resolution refinement of protein structure? Publishing Authors By Initials

J Chen,CL Brooks,

For similar proteins research abstracts see: proteins research

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Can molecular dynamics simulations provide high-resolution refinement of protein structure? Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Proteins

VOLUME: 67

Page Numbers: 922-30

Journal Abbreviation: Proteins

ISSN: 1097-0134

DAY: 1

MONTH: Jun

YEAR: 2007

Can molecular dynamics simulations provide high-resolution refinement of protein structure? Information

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LANGUAGE: eng

NlmUniqueID: 8700181

Can molecular dynamics simulations provide high-resolution refinement of protein structure? Keywords Mesh Terms:

KEYWORDS: Proteins

MESH TERMS: chemistry

Chemical & Substance for Abstract: Can molecular dynamics simulations provide high-resolution refinement of protein structure? Information

Substance Name: Proteins

Registry Number: 0

Grant and Affiliation Information for Can molecular dynamics simulations provide high-resolution refinement of protein structure?

AFFILIATION: Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.

Country: United States

AGENCY: United States NCRR

GRANT: RR12255

ACRONYM: RR

MEDLINETA: Proteins

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