|Authors||P. M. Kekenes-Huskey, A. K. Gillette, J. E. Hake and A. J. McCammon|
|Title||Finite-Element Estimation of Protein-ligand Association Rates With Post-Encounter Effects: Applications to Calcium Binding in Troponin C and SERCA|
|Afilliation||, Scientific Computing, Scientific Computing|
|Project(s)||Center for Biomedical Computing (SFF)|
|Publication Type||Journal Article|
|Year of Publication||2012|
|Journal||Computational Science & Discovery|
We introduce a computational pipeline and suite of software tools for the approximation of diffusion-limited binding based on a recently developed theoretical framework. Our approach handles molecular geometries generated from high-resolution structural data and can account for active sites buried within the protein or behind gating mechanisms. Using tools from the FEniCS library and the APBS solver, we implement a numerical code for our method and study two Ca2+-binding proteins: troponin C and the sarcoplasmic reticulum Ca2+ ATPase. We find that a combination of diffusional encounter and internal 'buried channel' descriptions provides superior descriptions of association rates, improving estimates by orders of magnitude.