Potential-Energy and Free-Energy Surfaces of Glycyl-Phenylalanyl-Alanine (GFA) Tripeptide. Experiment and Theory
- Academy of Sciences of the Czech Republic (ASCR), Prague (Czech Republic)
- Inst. of Chemical Technology of Prague (Czech Republic)
- Univ. of Leeds (United Kingdom)
- 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 Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC05-76RL01830
- OSTI ID:
- 959193
- Journal Information:
- Chemistry - A European Journal, Vol. 14, Issue 16; ISSN 0947-6539
- Publisher:
- ChemPubSoc Europe
- Country of Publication:
- United States
- Language:
- English
Similar Records
Benchmark Database on Isolated Small Peptides Containing an Aromatic Side Chain: Comparison Between Wave Function and Density Functional Theory Methods and Empirical Force Field
Conformational Changes Induced by Methyl Side-Chains in Protonated Tripeptides Containing Glycine and Alanine Residues