Principal Investigator

S   Kuyucak Theoretical Physics, RSPhysSE, ANU

Project Title

Generalized Langevin Dynamics Approach to Modeling of Ion Channels

Brief Description for General Publications

Ion channels are formed by proteins in cell membranes and provide pathways for fast and controlled flow of selected ions. This process generates action potentials, which is crucial for normal function of neurons, muscles and other excitable cells. Many neurological and muscular disorders are caused by malfunctioning of ion channels due to mutations in the genes that transcript the channel proteins. To develop therapeutic drugs that target such channels, one needs to understand their function in terms of dynamical models. At present, Brownian dynamics provides the most promising approach for this purpose. However, the Langevin equation (LE) employed in Brownian dynamics simulations is strictly valid for Brownian particles that are much heavier than the surrounding water molecules, which is not satisfied by ions. Another potential problem is the use of very short time steps in the channel (in order to sample the forces accurately), which may invalidate the Markovian assumption of the Langevin equation. Both of these problems can be studied using the generalized Langevin equation (GLE), where the memory effects are included in the friction and random forces. In this project we aim to develop the GLE approach for ion channels and carry out extensive tests to check the validity of the LE. If the LE is found to lead to substantially different results for channel observables compared to those of the GLE, it will be replaced by the GLE algorithm in the Brownian dynamics code.