Finite-element estimation of protein-ligand association rates with post-encounter effects: Applications to calcium binding in troponin C and SERCA

P. M. Kekenes-Huskey, A. Gillette, J. Hake, J. A. McCammon

Research output: Contribution to journalArticle

15 Scopus citations

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 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.

Original languageEnglish (US)
Article number014015
JournalComputational Science and Discovery
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • Numerical Analysis
  • Physics and Astronomy(all)
  • Computational Mathematics

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