A semi‐implicit solvent model for the simulation of peptides and proteins

Abstract

We present a new model of biomolecules hydration based on macroscopic electrostatic theory, that can both describe the microscopic details of solvent–solute interactions and allow for an efficient evaluation of the electrostatic hydration free energy. This semi‐implicit model considers the solvent as an ensemble of polarizable pseudoparticles whose induced dipole describe both the electronic and orientational solvent polarization. In the presented version of the model, there is no mutual dipolar interaction between the particles, and they only interact through short‐ranged Lennard–Jones interactions. The model has been integrated into a molecular dynamics code, and offers the possibility to simulate efficiently the conformational evolution of biomolecules. It is able to provide estimations of the electrostatic solvation free energy within short time windows during the simulation. It has been applied to the study of two small peptides, the octaalanine and the N‐terminal helix of ribonuclease A, and two proteins, the bovine pancreatic trypsin inhibitor and the B1 immunoglobin‐binding domain of streptococcal protein G. Molecular dynamics simulations of these biomolecules, using a slightly modified Amber force field, provide stable and meaningful trajectories in overall agreement with experiments and all‐atom simulations. Correlations with respect to Poisson–Boltzmann electrostatic solvation free energies are also presented to discuss the parameterization of the model and its consequences. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1015–1029, 2004