Molecular dynamics simulations of peptide carboxylate hydration.

Aqueous solvation of carboxylate groups, as present in the glycine zwitterion and the dipeptide aspartylalanine, is studied employing a force-field that includes distributed multipole electrostatics and induction contributions (Amoebapro: P. Ren and J. W. Ponder, J. Comput. Chem., 2002, 23, 1497; P. Ren and J. W. Ponder, J. Phys. Chem. B, 2003, 107, 5933; J. W. Ponder and D. A. Case, Adv. Protein Chem., 2003, 66, 27). Radial and orientation distribution functions, as well as hydration numbers, are calculated and compared with existing simulation data derived from Car-Parrinello molecular dynamics (CPMD), and also distributed-charge force-fields. Connections are also made with experimental data for solvation of carboxylates in water. Our findings show that Amoebapro yields carboxylate solvation properties in very good agreement with CPMD results, significantly closer agreement than can be obtained from traditional force-fields. We also demonstrate that the influence of solvation on the conformation of the dipeptide is markedly different using Amoebapro compared with the other force-fields.