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Tertiary structure prediction of the KIX domain of CBP using Monte Carlo simulations driven by restraints derived from multiple sequence alignments
Author(s) -
Ortiz Angel R.,
Kolinski Andrzej,
Skolnick Jeffrey
Publication year - 1998
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(19980215)30:3<287::aid-prot8>3.0.co;2-h
Subject(s) - monte carlo method , sequence (biology) , statistical physics , domain (mathematical analysis) , computer science , physics , algorithm , mathematics , chemistry , statistics , mathematical analysis , biochemistry
Using a recently developed protein folding algorithm, a prediction of the tertiary structure of the KIX domain of the CREB binding protein is described. The method incorporates predicted secondary and tertiary restraints derived from multiple sequence alignments in a reduced protein model whose conformational space is explored by Monte Carlo dynamics. Secondary structure restraints are provided by the PHD secondary structure prediction algorithm that was modified for the presence of predicted U‐turns, i.e., regions where the chain reverses global direction. Tertiary restraints are obtained via a two‐step process: First, seed side‐chain contacts are identified from a correlated mutation analysis, and then, a threading‐based algorithm expands the number of these seed contacts. Blind predictions indicate that the KIX domain is a putative three‐helix bundle, although the chirality of the bundle could not be uniquely determined. The expected root‐mean‐square deviation for the correct chirality of the KIX domain is between 5.0 and 6.2 Å. This is to be compared with the estimate of 12.9 Å that would be expected by a random prediction, using the model of F. Cohen and M. Sternberg (J. Mol. Biol. 138:321–333, 1980). Proteins 30:287–294, 1998. © 1998 Wiley‐Liss, Inc.