\ Projects \ Biomolecular Modelling

The initial focus of this aspect of the project has been on developing more approximate approaches to voltage gated ion channels, with an aim to model cardiac Kv and related channels. Voltage-sensor toxins have been explored as a test system. This system is simpler than e.g. an intact Kv ion channel, yet requires good approximate methods if toxin/membrane interactions are to be captured correctly. Furthermore, there are good experimental data available for validation of the method. The experimental data have been supplemented by atomistic MD (AT-MD) simulations of the interactions of VSTx1 and SGTx1 with lipid bilayers. Coarse-grained (CG-MD) simulations of toxin/bilayer simulations have been performed and shown to be >100 x faster than AT-MD simulations. (These used a CG-MD method previously developed by the group). They have been compared with experimental data and AT-MD simulations and shown to yield comparable results.
Future work will pursue two main directions: (i) 'fast track': focusing on electrostatics and Brownian dynamics simulations of a cardiac Kir channel (Kir2.1) model; and (ii) 'deep track': development of methods to link e.g. elastic network models with Markov models of channel gating.