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Potential‐Energy and Free‐Energy Surfaces of Glycyl‐Phenylalanyl‐Alanine (GFA) Tripeptide: Experiment and Theory
Author(s) -
Valdes Haydee,
Spiwok Vojtech,
Rezac Jan,
Reha David,
AboRiziq Ali G.,
de Vries Mattanjah S.,
Hobza Pavel
Publication year - 2008
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200800085
Subject(s) - metadynamics , chemistry , ab initio , computational chemistry , conformational isomerism , potential energy surface , intramolecular force , density functional theory , ab initio quantum chemistry methods , potential energy , molecular dynamics , tripeptide , isomerization , crystallography , molecule , stereochemistry , atomic physics , physics , peptide , biochemistry , catalysis , organic chemistry
The free‐energy surface (FES) of glycyl‐phenylalanyl‐alanine (GFA) tripeptide was explored by molecular dynamics (MD) simulations in combination with high‐level correlated ab initio quantum chemical calculations and metadynamics. Both the MD and metadynamics employed the tight‐binding DFT‐D method instead of the AMBER force field, which yielded inaccurate results. We classified the minima localised in the FESs as follows: a) the backbone‐conformational arrangement; and b) the existence of a COOH⋅⋅⋅OC intramolecular H‐bond (families CO 2 H free and CO 2 H bonded ). Comparison with experimental results showed that the most stable minima in the FES correspond to the experimentally observed structures. Remarkably, however, we did not observe experimentally the CO 2 H bonded family (also predicted by metadynamics), although its stability is comparable to that of the CO 2 H free structures. This fact was explained by the former's short excited‐state lifetime. We also carried out ab initio calculations using DFT‐D and the M06‐2X functional. The importance of the dispersion energy in stabilising peptide conformers is well reflected by our pioneer analysis using the DFT‐SAPT method to explore the nature of the backbone/side‐chain interactions.