Presentations
Nonlinear dynamics of selectivity, conductivity, and gating in biological ion channels
Our main goal is to develop a novel Brownian dynamics (BD) description of channels by isolating biologically relevant degrees of freedom using molecular dynamics (MD), and to demonstrate theoretically and numerically that protein vibration, ion size and hydration at the selectivity filter, and charge fluctuations (all largely neglected in earlier work), provide leading order contributions to the channel's high conductivity and selectivity between ions of the same polarity. We now propose a full-scale research programme, building on the strong base of: (i) our EPSRC-funded (GR/S86174/01) preliminary project on BD simulations, Poisson-Nernst-Planck and reaction rate theories of ion channels; (ii) the Lancaster group's life-time expertise in non-equilibrium stochastic dynamics; (iii) their long-term collaboration with Rush University Medical College; and (iv) the international distinction and enormous experience of the Warwick group in MD simulation.
We will seek a self-consistent explanation of how strong selectivity between alike ions can be combined with high conductivity, stress relaxation and energy dissipation in the channel by developing a novel approach based on a combination of BD and MD simulations. We will also try to establish how coupling to the ion permeation via vibrations of the protein walls changes the energetics and statistics of the gating. Our theoretical and simulation results will be compared with real potassium, calcium, and artificial channel data in collaboration with experimentalists in Oxford, Chicago, Chapel Hill and Groningen.
Publications