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Derivation of protein‐specific pair potentials based on weak sequence fragment similarity
Author(s) -
Skolnick Jeffrey,
Kolinski Andrzej,
Ortiz Angel
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(20000101)38:1<3::aid-prot2>3.0.co;2-s
Subject(s) - threading (protein sequence) , gapless playback , protein superfamily , globular protein , similarity (geometry) , sequence (biology) , statistical potential , statistical physics , chemistry , computational biology , protein structure , biological system , physics , protein structure prediction , algorithm , biology , crystallography , genetics , computer science , artificial intelligence , biochemistry , image (mathematics) , gene , condensed matter physics
Abstract A method is presented for the derivation of knowledge‐based pair potentials that corrects for the various compositions of different proteins. The resulting statistical pair potential is more specific than that derived from previous approaches as assessed by gapless threading results. Additionally, a methodology is presented that interpolates between statistical potentials when no homologous examples to the protein of interest are in the structural database used to derive the potential, to a Go‐likepotential (in which native interactions are favorable and all nonnative interactions are not) when homologous proteins are present. For cases in which no protein exceeds 30% sequence identity, pairs of weakly homologous interacting fragments are employed to enhance the specificity of the potential. In gapless threading, the mean z score increases from −10.4 for the best statistical pair potential to −12.8 when the local sequence similarity, fragment‐based pair potentials are used. Examination of the ab initio structure prediction of four representative globular proteins consistently reveals a qualitative improvement in the yield of structures in the 4 to 6 Å rmsd from native range when the fragment‐based pair potential is used relative to that when the quasichemical pair potential is employed. This suggests that such protein‐specific potentials provide a significant advantage relative to generic quasichemical potentials. Proteins 2000;38:3–16. ©2000 Wiley‐Liss, Inc.