Conformational transitions of a dipeptide in water: Effects of imposed pathways using umbrella sampling techniques

Abstract

AbstractThe free energy difference between two states of a molecular system separated by an energy barrier can generally be computed using the technique of umbrella sampling along a chosen reaction coordinate or pathway. The effect of a particular choice of pathway upon the obtained free energy difference is investigated by molecular dynamics simulation of a model system consisting of a glycine dipeptide in aqueous solution. Two different reaction coordinates connecting the so‐called C5 and C7 conformations, one involving intramolecular hydrogen bonds and the other involving the peptide ϕ, ψ angles, are considered.The Gibbs free energy differences ΔG(C5 – C7) are small in both cases, 1.5 ± 1 kJ mol−1 and 2.2 ± 1 kJ mol −1, respectively. The two different reaction coordinates yield free energy differences that are identical to within their statistical error. It is found that the exchange of solute–solute, solute–water, and water–water hydrogen bonds involves free energy changes of less than kBT, which points at the existence of a multitutde of low free energy pathways connecting the C5 and C7 dipeptide conformations. © 1994 John Wiley & Sons, Inc.