Conformational Dynamics of Trialanine in Water. 2. Comparison of AMBER, CHARMM, GROMOS, and OPLS Force Fields to NMR and Infrared Experiments

Abstract

Driven by recent two-dimensional infrared experiments by Woutersen and Hamm, trialanine has emerged as a paradigm to study conformational dynamics of a small peptide in aqueous solution. Employing the exceptional amount of experimental and ab initio data, in this work, trialanine serves as a model problem to perform a comprehensive comparison of six popular force fields, including the recent versions of the AMBER, CHARMM, GROMOS, and OPLS models. For all force fields under consideration, 20 ns long molecular-dynamics simulations are performed, and the structure and conformational dynamics of the solvated peptide is studied in detail. Employing density-functional theory calculations at the B3LYP/6-31+G(d) level, a number of observable quantities are calculated directly from the molecular-dynamics data and compared to experiment. The comparison allows for a quite detailed interpretation of recent NMR and infrared experiments. The nowadays achievable reliability and accuracy of a molecular dynamics description of a highly flexible biomolecular system are discussed in some detail.