Calculation of sequence-dependent free energies of hydration of dipeptidesformed by alanine and glycine

The relative free energies of hydration of the dipeptides glycylalanine and alanyl-glycine in their naturally occurring form have been calculated both for the zwitterionic and protonated species. Emphasis has laid on comparis ons between the conventional cutoff method and the Particle Mesh Ewald meth od to account for possible differences in electrostatic contributions to th e free energy Furthermore, the convergence behavior of the total free energ y and its individual contributions were examined. The results, obtained by means of the thermodynamic integration technique as implemented in the free energy module of: the AMBER program suite, suggest that in aqueous solutio n glycylalanine is more stable than alanylglycine by 2.7 kcal/mol in the zw itterionic form and by 3.5 kcal/mol in the protonated form. (C) 2001 John W iley & Sons, Inc.