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Refinement of protein termini in template‐based modeling using conformational space annealing
Author(s) -
Park Hahnbeom,
Ko Junsu,
Joo Keehyoung,
Lee Julian,
Seok Chaok,
Lee Jooyoung
Publication year - 2011
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.23101
Subject(s) - template , computer science , simulated annealing , loop modeling , protein structure prediction , algorithm , protein structure , function (biology) , biological system , data mining , chemistry , biology , programming language , biochemistry , evolutionary biology
The rapid increase in the number of experimentally determined protein structures in recent years enables us to obtain more reliable protein tertiary structure models than ever by template‐based modeling. However, refinement of template‐based models beyond the limit available from the best templates is still needed for understanding protein function in atomic detail. In this work, we develop a new method for protein terminus modeling that can be applied to refinement of models with unreliable terminus structures. The energy function for terminus modeling consists of both physics‐based and knowledge‐based potential terms with carefully optimized relative weights. Effective sampling of both the framework and terminus is performed using the conformational space annealing technique. This method has been tested on a set of termini derived from a nonredundant structure database and two sets of termini from the CASP8 targets. The performance of the terminus modeling method is significantly improved over our previous method that does not employ terminus refinement. It is also comparable or superior to the best server methods tested in CASP8. The success of the current approach suggests that similar strategy may be applied to other types of refinement problems such as loop modeling or secondary structure rearrangement. Proteins 2011; © 2011 Wiley‐Liss, Inc.