This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Song, Y. Articles by Baker, N. A. Search for Related Content PubMed PubMed Citation Articles by Song, Y. Articles by Baker, N. A.

Finite Element Solution of the Steady-State Smoluchowski Equation for Rate Constant Calculations

Yuhua Song ^*, Yongjie Zhang , Tongye Shen , Chandrajit L. Bajaj , J. Andrew McCammon ^¶ and Nathan A. Baker ^*

^* Department of Biochemistry and Molecular Biophysics, Center for Computational Biology, Washington University in St. Louis, St. Louis, Missouri; Institute for Computational Engineering and Sciences, Center for Computational Visualization, The University of Texas at Austin, Austin, Texas; Department of Chemistry and Biochemistry, Center for Theoretical Biological Physics, University of California at San Diego, La Jolla, California; Department of Computer Sciences and Institute for Computational Engineering and Sciences, Center for Computational Visualization, The University of Texas at Austin, Austin, Texas; and ^¶ Department of Chemistry and Biochemistry, Center for Theoretical Biological Physics, Department of Pharmacology, Howard Hughes Medical Institute, University of California at San Diego, La Jolla, California

Correspondence: Address reprint requests to Nathan A. Baker, Dept. of Biochemistry and Molecular Biophysics, Center for Computational Biology, Washington University in St. Louis, 700 S. Euclid Ave., Campus Box 8036, St. Louis, MO 63110. Tel.: 314-362-2040; Fax: 314-362-0234; E-mail: baker{at}biochem.wustl.edu.

This article describes the development and implementation of algorithms to study diffusion in biomolecular systems using continuum mechanics equations. Specifically, finite element methods have been developed to solve the steady-state Smoluchowski equation to calculate ligand binding rate constants for large biomolecules. The resulting software has been validated and applied to mouse acetylcholinesterase. Rates for inhibitor binding to mAChE were calculated at various ionic strengths with several different reaction criteria. The calculated rates were compared with experimental data and show very good agreement when the correct reaction criterion is used. Additionally, these finite element methods require significantly less computational resources than existing particle-based Brownian dynamics methods.

This article has been cited by other articles:

				Y. Cheng, C.-e. A. Chang, Z. Yu, Y. Zhang, M. Sun, T. S. Leyh, M. J. Holst, and J. A. McCammon Diffusional Channeling in the Sulfate-Activating Complex: Combined Continuum Modeling and Coarse-Grained Brownian Dynamics Studies Biophys. J., November 15, 2008; 95(10): 4659 - 4667. [Abstract] [Full Text] [PDF]

				Y. Cheng, J. K. Suen, D. Zhang, S. D. Bond, Y. Zhang, Y. Song, N. A. Baker, C. L. Bajaj, M. J. Holst, and J. A. McCammon Finite Element Analysis of the Time-Dependent Smoluchowski Equation for Acetylcholinesterase Reaction Rate Calculations Biophys. J., May 15, 2007; 92(10): 3397 - 3406. [Abstract] [Full Text] [PDF]

				C.-E. Chang, T. Shen, J. Trylska, V. Tozzini, and J. A. McCammon Gated Binding of Ligands to HIV-1 Protease: Brownian Dynamics Simulations in a Coarse-Grained Model Biophys. J., June 1, 2006; 90(11): 3880 - 3885. [Abstract] [Full Text] [PDF]

				J. Xing, H. Wang, and G. Oster From Continuum Fokker-Planck Models to Discrete Kinetic Models Biophys. J., September 1, 2005; 89(3): 1551 - 1563. [Abstract] [Full Text] [PDF]

				D. Zhang, J. Suen, Y. Zhang, Y. Song, Z. Radic, P. Taylor, M. J. Holst, C. Bajaj, N. A. Baker, and J. A. McCammon Tetrameric Mouse Acetylcholinesterase: Continuum Diffusion Rate Calculations by Solving the Steady-State Smoluchowski Equation Using Finite Element Methods Biophys. J., March 1, 2005; 88(3): 1659 - 1665. [Abstract] [Full Text] [PDF]