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Molecular dynamics simulations of a single tryptophan amino acid in water were performed with the CHARMM molecular mechanics program using the modified TIP3P, the refined SPC, and the original SPC/E water models. All these empirical water models are similar in nature, but small differences give significant differences in their properties for liquid water. Nanosecond molecular dynamics simulations were carried out in the NVT, NVE, or NPT ensembles using a cubic simulation cell furnished with periodic boundary conditions. The calculations of long-range interactions were performed with two different methods, the atom-based spherical cutoff method with force shifting, where the nonbonded interactions were smoothly shifted to zero at the cutoff distance, and the particle-mesh Ewald technique. Transition dipole autocorrelation functions and reorientation times of tryptophan were calculated and compared to experimental values. Tryptophan hydration was affected by the water model and the treatment of long-range electrostatic interactions. The reorientation time of tryptophan depended strongly on the water model used, and the viscosity of the model liquid was found to correlate with the tryptophan translational and rotational dynamics in water. Statistical accuracy and errors in the analyses are discussed.

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.