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Can a pairwise contact potential stabilize native protein folds against decoys obtained by threading?
Author(s) -
Vendruscolo Michele,
Najmanovich Rafael,
Domany Eytan
Publication year - 2000
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(20000201)38:2<134::aid-prot3>3.0.co;2-a
Subject(s) - decoy , threading (protein sequence) , pairwise comparison , parameterized complexity , perceptron , energy (signal processing) , gapless playback , computer science , function (biology) , algorithm , mathematics , protein structure , artificial intelligence , physics , chemistry , artificial neural network , biology , biochemistry , receptor , statistics , evolutionary biology , operating system , nuclear magnetic resonance
We present a method to derive contact energy parameters from large sets of proteins. The basic requirement on which our method is based is that for each protein in the database the native contact map has lower energy than all its decoy conformations that are obtained by threading. Only when this condition is satisfied one can use the proposed energy function for fold identification. Such a set of parameters can be found (by perceptron learning) if Mp , the number of proteins in the database, is not too large. Other aspects that influence the existence of such a solution are the exact definition of contact and the value of the critical distance Rc , below which two residues are considered to be in contact. Another important novel feature of our approach is its ability to determine whether an energy function of some suitable proposed form can or cannot be parameterized in a way that satisfies our basic requirement. As a demonstration of this, we determine the region in the ( Rc , Mp ) plane in which the problem is solvable, i.e., we can find a set of contact parameters that stabilize simultaneously all the native conformations. We show that for large enough databases the contact approximation to the energy cannot stabilize all the native folds even against the decoys obtained by gapless threading. Proteins 2000;38:134–148. © 2000 Wiley‐Liss, Inc.