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Confronting the problem of interconnected structural changes in the comparative modeling of proteins
Author(s) -
Samudrala Ram,
Pedersen Jan T.,
Zhou Huaibei,
Luo Rui,
Fidelis Krzysztof,
Moult John
Publication year - 1995
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.340230307
Subject(s) - computer science , sequence (biology) , spotting , context (archaeology) , variety (cybernetics) , protein structure , chain (unit) , biological system , artificial intelligence , algorithm , chemistry , biology , biochemistry , paleontology , physics , astronomy
Comparative models of three proteins have been built using a variety of computational methods, heavily supplemented by visual inspection. We consider the accuracy obtained to be worse than expected. A careful analysis of the models shows that a major reason for the poor results is the interconnectedness of the structural differences between the target proteins and the template structures they were modeled from. Side chain conformations are often determined by details of the structure remote in the sequence, and can be influenced by relatively small main chain changes. Almost all of the regions of substantial main chain conformational change interact with at least one other such region, so that they often cannot be modeled independently. Visual inspection is sometimes effective in correcting errors in sequence alignment and in spotting when an alternative template structure is more appropriate. We expect some improvements in the near future through the development of structure‐based sequence alignment tools, side chain interconnectedness rotamer choice algorithms, and a better understanding of the context sensitivity of conformational features. © 1995 Wiley‐Liss, Inc.