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Reversible peptide folding: Dependence on molecular force field used
Author(s) -
Damm Wolfgang,
van Gunsteren Wilfred F.
Publication year - 2000
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/(sici)1096-987x(20000715)21:9<774::aid-jcc6>3.0.co;2-5
Subject(s) - force field (fiction) , chemistry , opls , molecular dynamics , ab initio , folding (dsp implementation) , computational chemistry , melting point , potential energy , protein folding , helix (gastropod) , thermodynamics , crystallography , chemical physics , atomic physics , physics , water model , organic chemistry , ecology , biochemistry , engineering , quantum mechanics , snail , electrical engineering , biology
Temperature‐dependent nuclear magnetic resonance (NMR) and CD spectra of methanol solutions of a β‐heptapeptide have been interpreted in such a way that the secondary structure, a 3 14 ‐helix, is assumed to be stable in a temperature range of between 298 and 393 K. This is in contrast to the results of a 50‐ns molecular dynamics simulation using the G ROMOS 96 force field, which found a melting temperature of about 340 K. This discrepancy is addressed by further computational studies using the OPLS‐AA force field. The conformational energetics of N ‐formyl‐3‐aminobutanamide in vacuo are obtained using ab initio and density functional quantum‐mechanical calculations at the HF/6‐31G*, B3LYP/6‐31G*, and B3LYP/6‐311+G* levels of theory. The results permit development of torsional parameters for the OPLS‐AA force field that reproduce the conformational energetics of the monomer. By varying the development procedure, three parameter sets are obtained that focus on reproducing either low‐energy or high‐energy conformations. These parameter sets are tested by simulating the reversible folding of the β‐heptapeptide in methanol. The melting temperature of the helix formed (>360 K) is found to be higher than the one obtained from simulations using the G ROMOS 96 force field (∼340 K). Differences in the potential energy functions of the latter two force fields are evaluated and point to the origins of the difference in stability. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 774–787, 2000