Using DelPhi to Compute Electrostatic Potentials and Assess Their Contribution to Interactions
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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?Boltzmann (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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- Guidelines for Understanding Results
- Commentary
- Literature Cited
- Figures
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Basic Protocol 1:
Necessary Resources
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Figure 8.4.1 The Solute window. Assign the atomic charge, atomic radius, and solute dielectric here. For proteins, the dielectric constant ranges from 2.0 to 5.0. View Image -
Figure 8.4.2 The Solvent window. Set the solvent characteristics (i.e., Solvent Dielectric, Solvent Radius, Ionic Strength, and Ionic Radius) here. A dielectric constant of 80 and solvent radius of 1.4 Å is used for water. View Image -
Figure 8.4.3 The Grid window. DelPhi calculates electrostatic energy by mapping the molecule onto a three‐dimensional grid. The accuracy of the calculated electrostatic potentials depends heavily on the resolution of the grid. It is generally accepted that a grid resolution of 4 grid points/Å gives accurate enough results. View Image -
Figure 8.4.4 The Boundary window. Set grid boundaries here. The most common and recommended option is to use the Full_Coulombic choice. View Image -
Figure 8.4.5 The boundary window. The use of Focussing procedure requires two runs of Delphi program. In the first run, a potential map with a small Solute Extent (∼30%; Fig. ) is generated. This potential map file is used for the second run in which the Focussing is chosen as the boundary condition as shown in the figure. Higher Solute Extent (∼80%) could be chosen in the grid window during the second run. Also, the Auto_Get_Grid option must be turned on in the run window. View Image -
Figure 8.4.6 The Iterations window. Assign iteration characteristics here. Selecting Auto_Iterations allows the continuation of calculations until an energy convergence is reached. The user may also choose between a nonlinear and linear calculation by turning on or off the Non_Linear option, respectively. View Image -
Figure 8.4.7 The Files window. The necessary data (file outputs) needed should be chosen from the various options. View Image -
Figure 8.4.8 The Run DelPhi window. This command allows to specify the job details, such as to run as background or create an input file for command line submission at a later stage. View Image -
Figure 8.4.9 The potential map calculated for an α‐helix which has positively charged residues at the N terminus and negatively charged residues at the C‐terminus (sequence: RKHRRAAAAAADEDE). The potential map is plotted using the contour program available with insight II: −1 kcal/mole/e contour is displayed in red, and +1 kcal/mole/e contour is displayed in green. View Image
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Literature Cited
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| 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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