Potential-Energy and Free-Energy Surfaces of Glycyl-Phenylalanyl-Alanine (GFA) Tripeptide. Experiment and Theory

Journal Article · Thu Apr 17 04:00:00 EDT 2008 · Chemistry - A European Journal

DOI:https://doi.org/10.1002/chem.200800085· OSTI ID:959193

Valdes, Haydee ^[1]; Spiwok, Vojtech ^[2]; Rezac, Jan ^[1]; Reha, David ^[3]; Abo-Riziq, Ali G. ^[4]; de Vries, Mattanjah S. ^[4]; Hobza, Pavel ^[1]

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1. Academy of Sciences of the Czech Republic (ASCR), Prague (Czech Republic)
2. Inst. of Chemical Technology of Prague (Czech Republic)
3. Univ. of Leeds (United Kingdom)
4. Univ. of California, Santa Barbara, CA (United States)

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 tightbinding 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 CO₂Hfree and CO₂Hbonded). 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 CO₂Hbonded family (also predicted by metadynamics), although its stability is comparable to that of the CO₂Hfree 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 stabilizing peptide conformers is well reflected by our pioneer analysis using the DFT-SAPT method to explore the nature of the backbone/side-chain interactions.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States), Environmental Molecular Sciences Laboratory (EMSL)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 959193
• Journal Information: Chemistry - A European Journal, Journal Name: Chemistry - A European Journal Journal Issue: 16 Vol. 14; ISSN 0947-6539
• Publisher: ChemPubSoc Europe
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
59 BASIC BIOLOGICAL SCIENCES
CHEMICAL BONDS
EXCITED STATES
Environmental Molecular Sciences Laboratory
FREE ENERGY
MOLECULAR DYNAMICS METHOD
PEPTIDES
POTENTIAL ENERGY
STABILITY