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Titolo:
Free energies of protein decoys provide insight into determinants of protein stability
Autore:
Vorobjev, YN; Hermans, J;
Indirizzi:
Univ N Carolina, Sch Med, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA Univ N Carolina Chapel Hill NC USA 27599 ophys, Chapel Hill, NC 27599 USA
Titolo Testata:
PROTEIN SCIENCE
fascicolo: 12, volume: 10, anno: 2001,
pagine: 2498 - 2506
SICI:
0961-8368(200112)10:12<2498:FEOPDP>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
CONFORMATIONAL FREE-ENERGY; SOLVENT CONTINUUM MODEL; DYNAMICS SIMULATIONS; EXPLICIT SOLVENT; DISCRIMINATION; POLYPEPTIDES; PREDICTION; POTENTIALS; FOLDS; ES/IS;
Keywords:
protein conformation; free energy; scoring function; ES/IS method; implicit solvation model; molecular surface; electrostatic free energy; internal packing energy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Hermans, J Univ N Carolina, Sch Med, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA Univ N Carolina Chapel Hill NC USA 27599 el Hill, NC 27599 USA
Citazione:
Y.N. Vorobjev e J. Hermans, "Free energies of protein decoys provide insight into determinants of protein stability", PROTEIN SCI, 10(12), 2001, pp. 2498-2506

Abstract

We have calculated the stability of decoy structures of several proteins (from the CASP3 models and the Park and Levitt decoy set) relative to the native structures. The calculations were performed with the force field-consistent ES/IS method, in which an implicit solvent (IS) model is used to calculate the average solvation free energy for snapshots from explicit simulations (ESs). The conformational free energy is obtained by adding the internal energy of the solute from the ESs and an entropic term estimated from the covariance positional fluctuation matrix. The set of atomic Born radii and the cavity-surface free energy coefficient used in the implicit model hasbeen optimized to be consistent with the all-atom force field used in the ESs (cedar/gromos with simple point charge (SPC) water model). The decoys are found to have a consistently higher free energy than that of the native structure; the gap between the native structure and the best decoy varies between 10 and 15 kcal/mole, on the order of the free energy difference thattypically separates the native state of a protein from the unfolded state. The correlation between the free energy and the extent to which the decoy structures differ from the native (as root mean square deviation) is very weak; hence, the free energy is not an accurate measure for ranking the structurally most native-like structures from among a set of models. Analysis of the energy components shows that stability is attained as a result of three major driving forces: (1) minimum size of the protein-water surface interface: (2) minimum total electrostatic energy, which includes solvent polarization; and (3) minimum protein packing energy. The detailed fit required to optimize the last term may underlie difficulties encountered in recovering the native fold from an approximate decoy or model structure.

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Documento generato il 16/07/20 alle ore 20:00:23