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Titolo:
Determination of conformational equilibrium of peptides in solution by NMRspectroscopy and theoretical conformational analysis: Application to the calibration of mean-field solvation models
Autore:
Groth, M; Malicka, J; Rodziewicz-Motowidlo, S; Czaplewski, C; Klaudel, L; Wiczk, W; Liwo, A;
Indirizzi:
Univ Gdansk, Fac Chem, PL-80952 Gdansk, Poland Univ Gdansk Gdansk PolandPL-80952 sk, Fac Chem, PL-80952 Gdansk, Poland
Titolo Testata:
BIOPOLYMERS
fascicolo: 2, volume: 60, anno: 2001,
pagine: 79 - 95
SICI:
0006-3525(2001)60:2<79:DOCEOP>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
DRIVEN MONTE-CARLO; MULTIPLE-MINIMA PROBLEM; LOCAL TORSIONAL DEFORMATIONS; PANCREATIC TRYPSIN-INHIBITOR; ACCESSIBLE SURFACE-AREAS; MEMBRANE-BOUND PORTION; AMINO-ACIDS; NOE DATA; DISTANCE RESTRAINTS; ENERGY CALCULATIONS;
Keywords:
NMR; nuclear Overhauser effect; peptide conformation; solvation energy; global optimization;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
80
Recensione:
Indirizzi per estratti:
Indirizzo: Liwo, A Univ Gdansk, Fac Chem, Sobieskiego 18, PL-80952 Gdansk, Poland Univ Gdansk Sobieskiego 18 Gdansk Poland PL-80952 Gdansk, Poland
Citazione:
M. Groth et al., "Determination of conformational equilibrium of peptides in solution by NMRspectroscopy and theoretical conformational analysis: Application to the calibration of mean-field solvation models", BIOPOLYMERS, 60(2), 2001, pp. 79-95

Abstract

Peptides Occur in solution as ensembles of conformations rather than in a fixed conformation. The existing energy functions are usually inadequate topredict the conformational equilibrium in solution, because of failure to account properly for solvation, if the solvent is not considered explicitly(which is usually prohibitively expensive). NMR data are therefore widely incorporated into theoretical conformational analysis. Because of conformational flexibility, restrained molecular dynamics (with restraints derived from NMR data), which is usually applied to determine protein conformation is of limited use in the case of peptides. Instead, (a) the restraints are averaged within predefined time windows during molecular dynamics (AID) simulations (time averaging), (b) multiple-copy AID simulations are carried outand the restraints are averaged over the copies (ensemble averaging), or (c) a representative ensemble of sterically feasible conformations is generated and the weights of the conformations are then fitted so that the computed average observables match the experimental data (weight fitting). All these approaches are briefly discussed in this article. If an, adequate forcefield is used, conformations with large statistical weights obtained from the weight-fitting procedure should also have low energies, which can be implemented in force field calibration. Such a procedure is particularly attractive regarding the parameterization of the solvation energy in nonaqueoussolvents, e.g, dimethyl sulfoxide, for which thermodynamic solvation data are scarce. A method for calibration of solvation parameters in dimethyl sulfoxide, which is based Oil this principle was recently proposed by C Baysal and H. Meirovitch (Journal of the American Chemical Society, 1998, Vol. 120, pp. 800-812), in which the energy gap between the conformations compatible with NMR data and the alternative conformations is maximized, In this work, we propose an alternative method based on the principle that the best-fitting statistical weights of conformations should match the Boltzmann weights computed with the force field applied. Preliminary results obtained using three test peptides of varying conformational mobility: H-Ser(1)-Pro(2)-Lys(3)-Leu(4)-OH, Ac-Tyr(1)-D-Phe(2)-Ser(3)-Pro(4)-Lys(5)-Leu(6)-NH2, and cyclo(Tyr(1)-D-Phe(2)-Ser(3)-pro(4)-Lys(5)-Leu(6)) are presented. (C) 2001 John Wiley & Sons, Inc. Biopolymers (Pept Sci) 60: 79-95, 2001.

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Documento generato il 29/09/20 alle ore 17:14:20