Using DelPhi to Compute Electrostatic Potentials and Assess Their Contribution to Interactions

Assaf Oron1, Haim Wolfson1, Kannan Gunasekaran2, Ruth Nussinov3

1 Tel Aviv University, Tel Aviv, Israel, 2 Laboratory of Experimental and Computational Biology, National Cancer Institute, Frederick, Maryland, 3 Laboratory of Experimental and Computational Biology, SAIC‐Frederick, Frederick, Maryland
Publication Name:  Current Protocols in Bioinformatics
Unit Number:  Unit 8.4
DOI:  10.1002/0471250953.bi0804s02
Online Posting Date:  August, 2003
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Abstract

There is a general agreement that electrostatic interactions play a significant role in the structure and function of biological molecules. However, obtaining quantitative estimation of the electrostatic energy requires computational models that capture the microscopic nature of the heterogeneous environment of macromolecules. This protocol offers elaboration on one of the common methods to calculate the electrostatic energetic contributions using continuum electrostatics. The method involves solving the Poisson‚ÄźBoltzmann (PB) equation numerically and regarding the solute as having a homogenous dielectric constant. In order to apply this method, a three dimensional structure of the molecule derived from experimental data (crystallography, NMR) or modeling techniques is required. The protocol will focus on the DelPhi program (Accelrys Inc. San Diego), which is one of the most common programs used for the estimation of electrostatic free energy contribution. A simple procedure of assigning criteria and parameters (charge distribution, solvent and solute dielectric constants, iterations, grid resolution, etc) enables one to illustrate an electrostatic potential map and estimate the electrostatic free energy, although with limited accuracy.

     
 
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Table of Contents

  • Guidelines for Understanding Results
  • Commentary
  • Literature Cited
  • Figures
     
 
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Materials

Basic Protocol 1:

  Necessary Resources
      Hardware
  • Silicon Graphics IRIS workstations
      Software
  • Insight II modeling program and DelPhi module (Accelrys; see Internet Resources) or
  • DelPhi stand‐alone program (Columbia University; see Internet Resources)
      Files
  • Three‐dimensional structure of the unbound and bound proteins in PDB or other Insight II–readable format
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Figures

Videos

Literature Cited

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   Brooks, B.R., Bruccoleri, R.E., Olafson, B.D., States, D.J., Swaminathan, S., and Karplus, M. 1983. CHARMM: A program for macromolecular energy minimization and dynamic calculations. J. Comput. Chem. 4:187‐217.
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   Froloff, N., Windemuth, A., and Honig, B.H. 1997. On the calculation of binding free energies using continuum methods: Application to MHC class I protein‐peptide interactions. Protein Science 6:1293‐1301.
   Gilson, M.K. and Honig, B.H. 1986. The dielectric constant of a folded protein. Biopolymers 25:2097‐2119.
   Gilson, M.K. and Honig, B.H. 1988. Energetics of charge‐charge interactions in proteins. Proteins 3:32‐52.
   Honig, B.H., Sharp, K., and Yang, A.S. 1993. Macroscopic models of aqueous solution: Biological and chemical applications. J. Phys. Chem. 97:1101‐1109.
   Klapper, I., Hagstrom, R., Fine, R., Sharp, K., and Honig, B.H. 1986. Focusing of electric fields in the active site of Cu‐Zn superoxide dismutase: Effects of ionic strength and amino‐acid modification. Proteins 1:47‐59.
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   Nicholls, A. and Honig, B.H. 1991. A rapid finite difference algorithm, utilizing successive over‐relaxation to solve Poisson‐Boltzmann equations. J. Comput. Chem. 12:435‐445.
   Nielsen, J.E., Andersen, K.V., Honig, B., Hooft, R.W.W., Klebe, G., Vriend, G., and Wade, R.C. 1999. Improving macromolecular electrostatics calculations. Protein Eng. 12:657‐662.
   Pearlman, D.A. and Rao, G.B. 1998. Free energy calculation: Methods and applications. In The Encyclopedia of Computational Chemistry, vol. 2. (Schleyer, P.v.R., Jorgensen, W.L., Schaefer III, H.F., Schreiner, P.R., and Thiel, W., eds.), pp. 1053‐1058. John Wiley & Sons, Chichester, U.K.
   Rocchia, W., Alexov, E., and Honig, B. 2001. Extending the applicability of nonlinear Poisson‐Boltzmann equation: Multiple dielectric constants and multivalent ions. J. Phys. Chem. B. 105:6507‐6514.
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   Straatsma, T.P. and McCammon, J.A. 1991. Theoretical calculations of relative affinities of binding. Method Enzymol. 202:497‐511.
   Williams, D.H., Cox, J.P.L., Doig, A.J., Gardner, M., Gerhard. U., Kaye, P.T., Lal, A.R., Nicholls, I.A., Salter, C.J., and Mitchell, R.C. 1991. Toward the semiquantitative estimation of binding constants. Guides for peptide‐peptide binding in aqueous solution. J. Am. Chem. Soc. 113:7020‐7030.
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Key Reference
   Honig et al., 1993. See above.
  Covers the fundamental theoretical and practical aspects of DelPhi.
Internet Resources
   http://www.accelrys.com
  Accelrys Web site.
   http://trantor.bioc.columbia.edu/delphi
  Web site to obtain the source code of DelPhi program, available at the Department of Biochemistry, Columbia University.
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