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Generation of native-like protein structures from limited NMR data, modern force fields and advanced conformational sampling (2005)
| Venue: | J. Biomol. NMR |
| Citations: | 4 - 0 self |
BibTeX
@ARTICLE{Chen05generationof,
author = {Jianhan Chen and Hyung-sik Won and Wonpil Im and H. Jane Dyson and Charles L. Brooks Iii},
title = {Generation of native-like protein structures from limited NMR data, modern force fields and advanced conformational sampling},
journal = {J. Biomol. NMR},
year = {2005},
pages = {59--64}
}
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Abstract
structure refinement Determining an accurate initial native-like protein fold is one of the most important and time-consuming steps of de novo NMR structure determination. Here we demonstrate that high-quality native-like models can be rapidly generated from initial structures obtained using limited NOE assignments, through replica exchange molecular dynamics refinement with a generalized Born implicit solvent (REX/ GB). Conventional structure calculations using an initial sparse NOE set were unable to identify a unique topology for the zinc-bound C-terminal domain of E. coli chaperone Hsp33, due to a lack of unambiguous long range NOEs. An accurate overall topology was eventually obtained through labori-ous hand identification of long range NOEs. However we were able to obtain high-quality models with backbone RMSD values of about 2 A ̊ with respect to the final structures, using REX/GB refinement with the original limited set of initial NOE restraints. These models could then be used to make further assignments of ambiguous NOEs and thereby speed up the structure determination process. The ability to calculate accurate starting structures from the limited unambiguous NOE set available at the begin-ning of a structure calculation offers the potential of a much more rapid and automated process for
Keyphrases
modern force field conformational sampling native-like protein structure limited nmr data automated process zinc-bound c-terminal domain unique topology time-consuming step rex gb refinement structure refinement ambiguous no initial noe restraint final structure structure calculation long range no initial sparse noe set nmr structure determination original limited set high-quality native-like model replica exchange molecular dynamic refinement chaperone hsp33 limited unambiguous noe set limited noe assignment labori-ous hand identification unambiguous long range no conventional structure calculation initial structure high-quality model accurate overall topology rex gb accurate initial native-like protein fold structure determination process generalized born implicit solvent backbone rmsd value
