Estimating the Temperature Dependence of Peptide Folding Entropies and Free Enthalpies from Total Energies in Molecular Dynamics Simulations

• Published in: Chemistry : a European journal Vol. 14; no. 16; pp. 5039 - 5046
• Main Authors: Boned, Ricard, van Gunsteren, Wilfred F., Daura, Xavier
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 29.05.2008; WILEY‐VCH Verlag
• Subjects: GROMOS; Models, Molecular; molecular dynamics; peptide folding; peptides; Peptides - chemistry; Protein Folding; Temperature; Thermodynamics
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200701380

The temperature dependence of thermodynamic quantities, such as heat capacity, entropy and free enthalpy, may be obtained by using well‐known equations that relate these quantities to the enthalpy of the molecular system of interest at a range of temperatures. In turn, the enthalpy of a molecular system can be estimated from molecular dynamics simulations of an appropriate model. To demonstrate this, we have investigated the temperature dependence of the enthalpy, heat capacity, entropy and free enthalpy of a system that consists of a β‐heptapeptide in methanol and have used the statistical mechanics relationships to describe the thermodynamics of the folding/unfolding equilibrium of the peptide. The results illustrate the power of current molecular simulation force fields and techniques in establishing the link between thermodynamic quantities and conformational distributions. From conformational states to thermodynamics: Given sufficient sampling of conformational space, it is possible to calculate accurate system enthalpies from total energies in molecular dynamics simulations (see graphic). In turn, classical thermodynamics formulae provide a link between the temperature dependence of enthalpy and that of entropy and free enthalpy. This simple yet powerful analysis is presented in the context of peptide folding.