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Generalized comparative modeling (GENECOMP): A combination of sequence comparison, threading, and lattice modeling for protein structure prediction and refinement
Author(s) -
Kolinski A.,
Betancourt M.R.,
Kihara D.,
Rotkiewicz P.,
Skolnick J.
Publication year - 2001
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.1080
Subject(s) - threading (protein sequence) , protein structure prediction , computer science , cluster analysis , ab initio , algorithm , lattice (music) , casp , data mining , computational science , protein structure , artificial intelligence , physics , nuclear magnetic resonance , quantum mechanics , acoustics
An improved generalized comparative modeling method, GENECOMP, for the refinement of threading models is developed and validated on the Fischer database of 68 probe–template pairs, a standard benchmark used to evaluate threading approaches. The basic idea is to perform ab initio folding using a lattice protein model, SICHO, near the template provided by the new threading algorithm PROSPECTOR. PROSPECTOR also provides predicted contacts and secondary structure for the template‐aligned regions, and possibly for the unaligned regions by garnering additional information from other top‐scoring threaded structures. Since the lowest‐energy structure generated by the simulations is not necessarily the best structure, we employed two structure‐selection protocols: distance geometry and clustering. In general, clustering is found to generate somewhat better quality structures in 38 of 68 cases. When applied to the Fischer database, the protocol does no harm and in a significant number of cases improves upon the initial threading model, sometimes dramatically. The procedure is readily automated and can be implemented on a genomic scale. Proteins 2001;44:133–149. © 2001 Wiley‐Liss, Inc.