Years IV and V: MUSICO 3

We will combine the exact splitting of the time scales for the electrostatics of [6] to use a hierarchy of time steps corresponding to interactions of diverse ranges of locality. For example, H-bonds occur between 2.5-4Å, and in large systems overall structure may be given by very long range electrostatics. It is expected that much longer time steps will be possible, more than 3 orders of magnitude larger than for exact atomistic MD. This method will be used to study the gating mechanism of ion channels (even if not the whole mechanism, at least a significant portion of it). The handling of fast frequencies by MUSICO and Elber's reaction path methods will be compared.