Electrostatic Interaction Energy and Solvent Accessibility in the Methotrexate-Reduced Nicotinamide Adenine Dinucleotide Phosphate-Dihydrofolate Reductase Ternary Complex(Medicinal Chemistry,Chemical)
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The electrostatic interaction energies among dihydrofolate reductase (DHFR), coenzyme reduced nicotinamide adenine dinucleotide phosphate (NADPH) and methotrexate (MTX) were calculated by means of the Debye-Huckel equation taking the solvent accessibility into account; the results obtained were comparable with the experimental values. The atoms of guest molecules exposed on the molecular surface in NADPH and MTX may contribute to the electrostatic stabilization on the molecular complex formed with the host molecules. The electrostatic effects due to the replacement of charged amino acid residues with other ones or uncharged ones were visualized as the difference of two electrostatic correlation potentials by the use of computer graphics. It is shown that Arg43, Arg44, Arg57, and Asp26 of DHFR play important roles from the view point of electrostatic potential. A distance graphics method was used to express the distance from a patch on the van der Waals' surface of the guest molecule to the nearest host-molecular surface in order to visualize the buried ligand, and host-atom contacts with the guest atom are given as the contact ratio of the guest-atoms with the proper host atoms.
- Chemical & pharmaceutical bulletin
Chemical & pharmaceutical bulletin 35(5), 1880-1895, 1987-05-25
The Pharmaceutical Society of Japan