A. Pillardy et al., Recent improvements in prediction of protein structure by global optimization of a potential energy function, P NAS US, 98(5), 2001, pp. 2329-2333
Citations number
36
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Recent improvements of a hierarchical ab initio or de novo approach for pre
dicting both alpha and beta structures of proteins are described. The unite
d-residue energy function used in this procedure includes multibody interac
tions from a cumulant expansion of the free energy of polypeptide chains, w
ith their relative weights determined by Z-score optimization. The critical
initial stage of the hierarchical procedure involves a search of conformat
ional 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-en
ergy structures of the target proteins (ranging in size from 70 to 244 resi
dues) agreed with the experimental structures in many respects. The entire
experimental structure of a cyclic alpha -helical protein of 70 residues wa
s predicted to within 4.3 Angstrom alpha -carbon (C-alpha) rms deviation (r
msd) whereas, for other alpha -helical proteins, fragments of roughly 60 re
sidues were predicted to within 6.0 Angstrom C-alpha rmsd. Whereas beta str
uctures can now be predicted with the new procedure, the success rate for a
lpha/beta- and beta -proteins is lower than that for alpha -proteins at pre
sent. For the beta portions of alpha/beta structures, the C-alpha rmsd's ar
e less than 6.0 Angstrom for contiguous fragments of 30-40 residues; for on
e target, three fragments (of length 10, 23, and 28 residues, respectively)
formed a compact part of the tertiary structure with a C-alpha rmsd less t
han 6.0 Angstrom. Overall, these results constitute an important step towar
d the ab initio prediction of protein structure solely from the amino acid
sequence.