TY - JOUR
T1 - Finite-element estimation of protein-ligand association rates with post-encounter effects
T2 - Applications to calcium binding in troponin C and SERCA
AU - Kekenes-Huskey, P. M.
AU - Gillette, A.
AU - Hake, J.
AU - McCammon, J. A.
PY - 2012/1
Y1 - 2012/1
N2 - 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.
AB - 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.
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U2 - 10.1088/1749-4699/5/1/014015
DO - 10.1088/1749-4699/5/1/014015
M3 - Article
AN - SCOPUS:84870317105
SN - 1749-4680
VL - 5
JO - Computational Science and Discovery
JF - Computational Science and Discovery
IS - 1
M1 - 014015
ER -