Electro-Chemical Modeling Challenges of Biological Ion Pumps.

We outline the basic operational, structural and functional features of ion motive ATPases: transmembrane proteins central to biological functions of all animal cells. As an example we discuss the modeling problems associated with the operation of the surface membrane Na(+),K(+)-ATPase and skeletal muscle sarcoplasmic reticulum Ca(2+)-ATPase and focus on the frameworks required for their solution. There are three basic problems: identification of the pathway for ion permeation, prediction of ion binding rate coefficients and affinities based on the structure of the protein, and prediction of conformational changes of protein structure and the associated movement of charges within the membrane dielectric. A solution strategy useful in approaching the first two problems and preliminary results obtained using molecular dynamics simulations are also presented.