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Averaging interaction energies over homologs improves protein fold recognition in gapless threading
Author(s) -
Reva Boris A.,
Skolnick Jeffrey,
Finkelstein Alexei V.
Publication year - 1999
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(19990515)35:3<353::aid-prot9>3.0.co;2-e
Subject(s) - threading (protein sequence) , gapless playback , fold (higher order function) , physics , protein structure prediction , algorithm , crystallography , protein structure , chemistry , statistical physics , mathematics , computer science , condensed matter physics , nuclear magnetic resonance , programming language
Protein structure prediction is limited by the inaccuracy of the simplified energy functions necessary for efficient sorting over many conformations. It was recently suggested (Finkelstein, Phys Rev Lett 1998;80:4823–4825) that these errors can be reduced by energy averaging over a set of homologous sequences. This conclusion is confirmed in this study by testing protein structure recognition in gapless threading. The accuracy of recognition was estimated by the Z‐score values obtained in gapless threading tests. For threading, we used 20 target proteins, each having from 20 to 70 homologs taken from the HSSP sequence base. The energy of the native structures was compared with the energy from 34 to 75 thousand of alternative structures generated by threading. The energy calculations were done with our recently developed C α atom‐based phenomenological potentials. We show that averaging of protein energies over homologs reduces the Z‐score from ∼ −6.1 (average Z‐score for individual chains) to ∼ −8.1. This means that a correct fold can be found among 3 ∗ 10 9 random folds in the first case and among 3 ∗ 10 15 in the second. Such increase in selectivity is important for recognition of protein folds. Proteins 1999;35:353–359. © 1999 Wiley‐Liss, Inc.