Relative free energy of binding and binding mode calculations of HIV-1 RT inhibitors based on dock-MM-PB/GS

Proteins
Zhigang Zhou, Jeffry D Madura

Abstract

Tetrahydroimidazo-[4,5,l-jk][1,4]-benzodiazepin-2-(1H)-one (TIBO) derivatives are important nonnucleoside human immunodeficiency virus-1 reverse transcriptase inhibitors (NNRTI). Several TIBO derivatives have shown high potency to inhibit reverse transcriptase (RT) and one (Tivirapine) has entered into clinical trials. The free energy of binding (FEB) is a numerical way to express the binding affinity of a ligand to its receptor and has been applied in screening candidates in rational drug design. In this work, the FEB of 42 TIBOs in RT was studied. Relative FEB is expressed in the form of a linear combination of vdW, electrostatic, solvation, and nonpolar solvation energy terms. The predicted FEB activity of the TIBOs studied has a good correlation (r(2) = 0.8680, q(2) = 0.8298) with respect to the experimental activity (pIC(50)). Based on the data reported here, the Finite Difference Poisson Boltzmann with a Gaussian Smooth Dielectric Constant Function method (PB/GS) solvation energy term is very important in predicting the binding affinity of TIBOs in RT. In summary, the Dock-Molecular Mechanics (MM)-PB/GS method is a promising technique in predicting ligand/receptor binding affinity and it can be used to screen relatively l...Continue Reading

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Citations

Dec 29, 2007·Journal of Computer-aided Molecular Design·Nitin S SapreNeelima Sapre
Jan 5, 2007·Physical Chemistry Chemical Physics : PCCP·Niu HuangMatthew P Jacobson
Feb 24, 2015·Journal of Biomolecular Structure & Dynamics·Martin González-AndradeImilla I Arias-Olguín
Mar 5, 2011·Journal of Computational Chemistry·Hannes G WallnoeferThomas Fox
Dec 15, 2010·Bioorganic & Medicinal Chemistry·Prashi JainJeffry D Madura
Apr 20, 2017·Journal of Natural Products·Laura Flores-BocanegraRachel Mata
Aug 4, 2018·Cell Biochemistry and Biophysics·Kgothatso E MachabaMahmoud E S Soliman
Jul 19, 2018·The Journal of Antibiotics·Daniela Rebollar-RamosRachel Mata
Oct 27, 2020·Journal of Biomolecular Structure & Dynamics·Joyce Oloaigbe OgidigoMahmoud E S Soliman
Oct 31, 2020·Journal of Biomolecular Structure & Dynamics·Alejandro Sosa-PeinadoMartin González-Andrade
Dec 3, 2020·Genes·Edgar Turrubiartes-MartínezElena Fernández-Ruiz
Feb 2, 2021·Phytochemistry·Miriam Díaz-RojasRachel Mata
Aug 18, 2010·Journal of Chemical Information and Modeling·Kanin WichapongWolfgang Sippl

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