Finite Element Estimation of Protein-Ligand Association Rates with Post-Encounter Effects: Applications to Calcium binding in Troponin C and SERCA.
Author | |
---|---|
Abstract | :
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 Ca(2+)-binding proteins: Troponin C and the Sarcoplasmic Reticulum Ca(2+) ATPase (SERCA). We find that a combination of diffusional encounter and internal 'buried channel' descriptions provide superior descriptions of association rates, improving estimates by orders of magnitude. |
Year of Publication | :
2012
|
Journal | :
Computational science & discovery
|
Volume | :
5
|
Date Published | :
2012
|
DOI | :
10.1088/1749-4699/5/1/014015
|
Short Title | :
Comput Sci Discov
|
Download citation |