Molecular dynamics simulations of the Ala-Pro dipeptide in water: Conformational dynamics of trans and cis isomers using different water models

Molecular dynamics simulations of a single dipeptide (Ala-Pro) molecule in water were carried out using different water models, the modified TIP3P (transferable intermolecular potential 3P), the refined SPC (simple point charge), and the original SPC/E (extended simple point charge). Both trans and cis isomers of the dipeptide were simulated, and conformations from simulations with the different water models were compared. Both isomers have several conformations, but the total conformational space is limited. Two experimentally obtained subconformations of the cis isomer were found in simulations with the different water models. The bioactive conformation, which is binding to Cyclophilin A, was the major cis conformation, and the conformation with an intramolecular hydrogen bond between the N-terminal and the C-terminal was found to exist as the minor cis conformation. The hydration of the dipeptide was found to depend both on its conformation and on the water model.