Calculations of the electrostatic free energy contributions to the binding free energy of sulfonamides to carbonic anhydrase

Jeffry D. Madura, Yasushi Nakajima, Rodney M. Hamilton, Andrzej Wierzbicki, Arieh Warshel

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

The interactions between biologically important enzymes and drugs are of great interest. In order to address some aspects of these interactions we have initiated a program to investigate enzyme-drug interactions. Specifically, the interactions between one of the isozymes of carbonic anhydrase and a family of drugs known as sulfonamides have been studied using computational methods. In particular the electrostatic free energy of binding of carbonic anhydrase II with acetazolamide, methazolamide, p-chlorobenzenesulfonamide, p-aminobenzenesulfonamide and three new compounds (MK1, MK2, and MK3) has been computed using finite-difference Poisson-Boltzmann (FDPB) [1] method and the semimacroscopic version [2, 3] of the protein dipole Langevin dipole (PDLD) method [4]. Both methods, FDPB and PDLD, give similar results for the electrostatic free energy of binding even though different charges and different treatments were used for the protein. The calculated electrostatic binding free energies are in reasonable agreement with the experimental data. The potential and the limitation of electrostatic models for studies of binding energies are discussed.

Original languageEnglish
Pages (from-to)131-138
Number of pages8
JournalStructural Chemistry
Volume7
Issue number2
DOIs
Publication statusPublished - 1996 Apr
Externally publishedYes

ASJC Scopus subject areas

  • Condensed Matter Physics
  • Physical and Theoretical Chemistry

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