Free Energy Calculations of Conformational Equilibrium of Chorismate in Water. The Role of Solute Polarization

Abstract

The conformational equilibrium of chorismate molecule in water has been studied with Monte Carlo free energy perturbation simulations. Relative solvation free energies of chorismate conformations have been calculated using three types of perturbation paths depending on the intermolecular solute−solvent energy terms considered. First, smooth transformation between solute conformations are performed without consideration of chorismate site charges. Second, the solvation free energy contribution because of the inclusion of electrostatic solute−solvent interactions are calculated. Finally, the role of polarization forces are studied introducing progressively atom polarizabilities in the chorismate molecule. The calculation of relative free energies through these three perturbation paths allows the comparison of the different energetic forces, and improves the convergence of the results. It has been found that the inclusion of solute polarization is crucial to obtain diequatorial−diaxial conformational proportions compatible with the experimental values. Different procedures to calculate solute polarization are analyzed depending on the way the intramolecular interactions among the polarization sites of chorismate are treated. Two types of water models, polarizable and nonpolarizable, have been considered. A hydrogen bond analysis and a study of the role of the charge variations among chorismate conformations are also done.