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Contact prediction for beta and alpha‐beta proteins using integer linear optimization and its impact on the first principles 3D structure prediction method ASTRO‐FOLD
Author(s) -
Rajgaria R.,
Wei Y.,
Floudas C. A.
Publication year - 2010
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/prot.22696
Subject(s) - protein structure prediction , protein tertiary structure , protein structure , test set , residue (chemistry) , integer (computer science) , energy minimization , mathematics , biological system , algorithm , chemistry , computer science , biology , statistics , computational chemistry , biochemistry , programming language
Abstract An integer linear optimization model is presented to predict residue contacts in β, α + β, and α/β proteins. The total energy of a protein is expressed as sum of a C α C α distance dependent contact energy contribution and a hydrophobic contribution. The model selects contact that assign lowest energy to the protein structure as satisfying a set of constraints that are included to enforce certain physically observed topological information. A new method based on hydrophobicity is proposed to find the β‐sheet alignments. These β‐sheet alignments are used as constraints for contacts between residues of β‐sheets. This model was tested on three independent protein test sets and CASP8 test proteins consisting of β, α + β, α/β proteins and it was found to perform very well. The average accuracy of the predictions (separated by at least six residues) was ∼61%. The average true positive and false positive distances were also calculated for each of the test sets and they are 7.58 Å and 15.88 Å, respectively. Residue contact prediction can be directly used to facilitate the protein tertiary structure prediction. This proposed residue contact prediction model is incorporated into the first principles protein tertiary structure prediction approach, ASTRO‐FOLD. The effectiveness of the contact prediction model was further demonstrated by the improvement in the quality of the protein structure ensemble generated using the predicted residue contacts for a test set of 10 proteins. Proteins 2010. © 2010 Wiley‐Liss, Inc.