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| Title: | FINITE ELEMENT ANALYSIS OF DRUG ELECTROSTATIC DIFFUSION: INHIBITION RATE STUDIES IN N1 NEURAMINIDASE | |
| DOI No: | 10.1142/9789812836939_0027 | |
| Source: | BIOCOMPUTING 2009 (pp 281-292) | |
| Author(s): | YUHUI CHENG
Uinversity of California, San Diego 9500 Gilman Dr.MC 0365, La Jolla, CA 92037, USA MICHAEL J. HOLST Uinversity of California, San Diego 9500 Gilman Dr.MC 0365, La Jolla, CA 92037, USA J. A. MCCAMMON This work is supported by nih gm31749, nsf mcb-0506593 and mca93s013 (to jam). additional support from the howard hughes medical institute, the nsf supercomputer centers, the san diego supercomputing center, accelrys, inc., the w.m. keck foundation, the national biomedical computational resource and the center for theoretical biological physics is gratefully acknowledged. Uinversity of California, San Diego 9500 Gilman Dr.MC 0365, La Jolla, CA 92037, USA |
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| Abstract: | This article describes a numerical solution of the steady-state Poisson-Boltzmann-Smoluchowski (PBS) and Poisson-Nemst-Planck (PNP) equations to study diffusion in biomolecular systems. Specifically, finite element methods have been developed to calculate electrostatic interactions and ligand binding rate constants for large biomolecules. The resulting software has been validated and applied to the wild-type and several mutated avian influenza neurominidase crystal structures. The calculated rates show very good agreement with recent experimental studies. Furthermore, these finite element methods require significantly fewer computational resources than existing particle-based Brownian dynamics methods and are robust for complicated geometries. The key finding of biological importance is that the electrostatic steering plays the important role in the drug binding process of the neurominidase. | |
| Full Text: | View full text in PDF format (1588KB) | |
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