9630475 Schumaker The objective of this research is to develop a class of theories (called "synchronous diffusions") of ion permeation through membrane channels. The idea of a synchronous diffusion is that, due to packing or other constraints, several molecules together may undergo a coordinated diffusive motion with only one important degree of freedom. Like discrete state (rate theory) models, synchronous diffusions are constructed to incorporate constraints on ion occupation needed for theories of multi-ion permeation. In contrast to discrete state models, however, they provide a truly diffusive description of transport. A synchronous diffusion describing single-ion conductance has already been developed, and this project now considers four more complicated cases: (1) permeation of a single ion species through a two-site single-vacancy channel, (2) permeation through a two-site single-vacancy channel under bi-ionic conditions, (3) permeation of a single ion species through a three- barrier-two-site double-occupancy channel, and (4) permeation through a single-ion channel with waters explicitly represented. %%% The goal is to develop theories of the motion of biomolecular systems that can serve as a bridge between the results of computer simulations and experiment. In particular, these theories will be developed to describe how ions can pass through certain protein molecules, known as "membrane channels", which are found in cell membranes. The need for bridging theories arises from two important developments in molecular biophysics. The first of these is that information about the detailed 3D structure of molecules makes it possible to simulate molecular motions on a computer. The second development is that experimental techniques are able to explore how things move on the molecular level. However, due to limited computer power, the simulated times are much shorter than those required to make direct comparisons with experiment. The bridging theories descried in this proposal wi ll be able to use the results of the computer simulations to compute quantities which can be compared with experiment. ***
