期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2001
卷号：98
期号：5
页码：2329-2333
DOI：10.1073/pnas.041609598
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Recent improvements of a hierarchical ab initio or de novo approach for predicting both and {beta} structures of proteins are described. The united-residue energy function used in this procedure includes multibody interactions from a cumulant expansion of the free energy of polypeptide chains, with their relative weights determined by Z-score optimization. The critical initial stage of the hierarchical procedure involves a search of conformational space by the conformational space annealing (CSA) method, followed by optimization of an all-atom model. The procedure was assessed in a recent blind test of protein structure prediction (CASP4). The resulting lowest-energy structures of the target proteins (ranging in size from 70 to 244 residues) agreed with the experimental structures in many respects. The entire experimental structure of a cyclic -helical protein of 70 residues was predicted to within 4.3 A -carbon (C) rms deviation (rmsd) whereas, for other -helical proteins, fragments of roughly 60 residues were predicted to within 6.0 A C rmsd. Whereas {beta} structures can now be predicted with the new procedure, the success rate for /{beta}- and {beta}-proteins is lower than that for -proteins at present. For the {beta} portions of /{beta} structures, the C rmsd's are less than 6.0 A for contiguous fragments of 30-40 residues; for one target, three fragments (of length 10, 23, and 28 residues, respectively) formed a compact part of the tertiary structure with a C rmsd less than 6.0 A. Overall, these results constitute an important step toward the ab initio prediction of protein structure solely from the amino acid sequence.
