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Relative free energy of binding and binding mode calculations of HIV‐1 RT inhibitors based on dock‐MM‐PB/GS
Author(s) -
Zhou Zhigang,
Madura Jeffry D.
Publication year - 2004
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20223
Subject(s) - solvation , ligand (biochemistry) , chemistry , binding energy , binding site , receptor , computational chemistry , molecule , physics , atomic physics , biochemistry , organic chemistry
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 large sets of molecules in a reasonable amount of computer time. Proteins 2004. © 2004 Wiley‐Liss, Inc.