Multi-scale models of solute and ion transport in membrane proteins and artificial nanopores

点击翻译按钮获取中文摘要

The main theme of the proposed research program is the development and application of modern modelling approaches to understanding of solute transport in membrane proteins and nanopores. There are many sophisticated experimental methods to measure aspects of the behavior, shape, and interactions of molecules with nanopores and membrane proteins. Molecular machinery controlling specific ion and solute transport is the major component of cell-regulatory systems, which defines delivery routes for nutrients and osmolytes, cell signaling and generation of biological electricity. The trans-membrane proteins define remarkable mechanical and electrical properties of biological membranes, displaying surprisingly complex physical behavior and selectivity (ability to sort solutes) at or near diffusion limits. The dynamics of transport proteins is intimately coupled, via yet unknown mechanisms, to the specific cargo they are moving across the cell membranes. The various membrane proteins were used in the past in direct biotechnology applications and as templates for bio-inspired materials (proton nanowires for example). The size of the system and multiple confounding factors of the complex cellular environment represent substantial challenges interpreting molecular mechanisms of solute transport from experimental observations alone. Using powerful computers and a description of how atoms interact with each other, it is possible to calculate in atomic detail how biomolecules move and interact in time. This research project is aimed at developing and applying computational models of molecules to better understand the thermodynamics and kinetics of solute transport in narrow and wide biological pores. We have made significant progress in developing theories and methods for effective sampling of free energy surfaces, as well as developing methods for direct modelling and interpretations of experimental data on nanopores. We are in a unique position to study transport processes at various levels of resolution from electronic degrees of freedom relevant to proton transport to mesoscopic-level studies of DNA passage through a nanopore. Our main interest is how to relate pore/protein structure to specific transport function in a number of model systems spanning from ion/proton transport in proton channels to solute-controlled dynamics of secondary transporters to DNA and metabolite passage through biological and artificial nanopores. The proposed studies will allow a prospective combination of cutting-edge simulation data and experimental studies combining biological spectroscopy, neutron diffraction studies, solid-state NMR and electrophysiology.