Finite Element Estimation of Protein-Ligand Association Rates with Post-Encounter Effects: Applications to Calcium binding in Troponin C and SERCA.
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Abstract |
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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 |
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2012
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Journal |
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Computational science & discovery
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Volume |
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5
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Date Published |
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2012
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DOI |
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10.1088/1749-4699/5/1/014015
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Short Title |
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Comput Sci Discov
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