Perturbation-Relaxation Molecular Dynamics Simulations as a Tool to Explore Conformational Space. Reversible Response of the L3 Loop in Porin Towards Charge Screening Effects

Abstract

A molecular dynamics perturbation-relaxation method is proposed for sensing the response of MD-equilibrated structures to external perturbing conditions. The procedure permits a searching of conformations that are interconvertible with a given structure when the external perturbation is switched off. In this way, it is possible to exploit the intrinsic information of the structure to find new conformations of interest following paths between them that might be accessible at low temperature. In the example reported, the external perturbation is produced by a change in membrane potential. A model is built to mimic this circumstance and the nature of the molecular system, a porin protein. The relaxation time is speeded up by using the GROMOS electroneutral and collisionless MD force field that has been fairly sucessful in representing X-ray and NMR determined structures. Using an electrostatic perturbation we found molecular determinants for a possible mechanism leading to pore closure in porins. The response of the L3-loop correlates well with or previous flexibility studies.