ISSN:
0887-3585
Keywords:
drug design
;
receptor-ligand interaction
;
computer simulation
;
solvation energy
;
desolvation energy
;
Chemistry
;
Biochemistry and Biotechnology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Medicine
Notes:
A practical method to estimate binding free energy, ΔGbind, of a given ligand structure to the target receptor has been developed. The method assumes that ΔGbind is given by the summation of intermolecular interaction energy, ΔGinter, and partial desolvation energy, ΔGdesolv. ΔGdesolv is calculated from the buried surface area in the complex between the ligand and receptor, based on solvation energy, ΔGsolv, formulated by an equation which can be calibrated with observed values. Then, the method was applied to arabinose-binding protein (ABP) and dihydrofolate reductase (DHFR), after recalibrating the weights for ΔGinter and each term of ΔGdesolv using observed ΔGbind data for 29 known ligands to avidin (AV). The usefulness of our method was confirmed by the fact that correlation coefficients between the calculated and observed ΔGbind's in AV, ABP and DHFR were 0.92, 0.77, and 0.88, whereas the corresponding values obtained by simple force field calculation were 0.79, 0.30, and 0.79, respectively. Further investigations to improve the method and validate the parameters are in progress. Proteins 33:62-73, 1998. © 1998 Wiley-Liss, Inc.
Additional Material:
10 Ill.
Type of Medium:
Electronic Resource
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