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Proteins that control and guide the transport of electrons, protons and ions, underpin the basic functions of living cells, and are crucial to many life processes. This includes the generation of chemical energy by using electron transfer (ET) and proton transport (PTR) to produce electrochemical gradients across membranes, which are then used to produce ATP. Similarly, a vital role in neural signal transduction and other functions is played by ion channels. Since mutations that disrupt the action of these proteins are associated with many diseases, these proteins present major targets for therapeutic intervention and play a central role in drug discovery efforts. However, despite spectacular progress in the structural elucidation and biochemical characterization of the above systems, a quantitative understanding of the factors that control the operation of such systems is still needed. A better understanding of the function of such systems should help in the development of drugs against serious diseases. Thus, it is important to develop, refine and apply quantitative structure-function correlations using computer simulation approaches. To understand such a complex dynamical system the constructive approach of computer simulation is proposed
Warshel has pioneered consistent microscopic and semimacroscopic simulations of the energetics of ion channels [1] as well as the key concepts and approaches in modeling proton transport in proteins [2] [3] [4]. Our approaches range from fully microscopic charging FEP and EVB simulations of proton transfer barriers to renormalization CG Langavin dynamics simulations of proton transport and ion transfer in proteins and solutions [5]. Our use of CG models allow us to ask questions which are in the forefront of the field such as the nature of the gating current in voltage activated ion channels [6] and the control of proton transport in biological systems such as Cytocrome c Oxidase and F0-ATPase.
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