Design of hybrid inhibitors to HIV-1 protease

Da W. Zhang, Philip Lin Huang, Sylvia Lee-Huang, John Zhang

Research output: Contribution to journalArticle

Abstract

A series of HIV-1 protease (PR) inhibitors are designed to increase the binding affinity with PR subsites based on the quantum analysis of the contributions of molecular fragments in six FDA-approved PR drugs to the total binding interaction. The binding free energies were estimated by modified linear interaction energy approach [Zoete H, Michielin O, Karplus M, J Comput Aided Mol Des 17:861, 2003], in which the binding free energy is written as a linear combination of the electrostatic interaction energy between PR and the ligand, Eelec, the van der Waals interaction energy between PR and the ligand, EvdW, and the difference of the solvation free energies of the complex, the receptor and the isolated ligand, ΔGsolv. The parameters of these energy terms were fitted for a training set of 14 HIV-1 protease-inhibitor complexes of known 3D structure with a correlation coefficient of 0.91 and an unsigned mean error of 0.83 kcal/mol.

Original languageEnglish (US)
Pages (from-to)485-503
Number of pages19
JournalJournal of Theoretical and Computational Chemistry
Volume7
Issue number4
DOIs
StatePublished - Aug 2008

Fingerprint

protease
human immunodeficiency virus
inhibitors
Peptide Hydrolases
Free energy
Ligands
Protease Inhibitors
free energy
ligands
Solvation
Coulomb interactions
interactions
energy
correlation coefficients
solvation
affinity
Human immunodeficiency virus 1 p16 protease
drugs
education
fragments

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry

Cite this

Design of hybrid inhibitors to HIV-1 protease. / Zhang, Da W.; Huang, Philip Lin; Lee-Huang, Sylvia; Zhang, John.

In: Journal of Theoretical and Computational Chemistry, Vol. 7, No. 4, 08.2008, p. 485-503.

Research output: Contribution to journalArticle

Zhang, Da W. ; Huang, Philip Lin ; Lee-Huang, Sylvia ; Zhang, John. / Design of hybrid inhibitors to HIV-1 protease. In: Journal of Theoretical and Computational Chemistry. 2008 ; Vol. 7, No. 4. pp. 485-503.
@article{ca75088e2dc74043a170fc4f6d9cde29,
title = "Design of hybrid inhibitors to HIV-1 protease",
abstract = "A series of HIV-1 protease (PR) inhibitors are designed to increase the binding affinity with PR subsites based on the quantum analysis of the contributions of molecular fragments in six FDA-approved PR drugs to the total binding interaction. The binding free energies were estimated by modified linear interaction energy approach [Zoete H, Michielin O, Karplus M, J Comput Aided Mol Des 17:861, 2003], in which the binding free energy is written as a linear combination of the electrostatic interaction energy between PR and the ligand, Eelec, the van der Waals interaction energy between PR and the ligand, EvdW, and the difference of the solvation free energies of the complex, the receptor and the isolated ligand, ΔGsolv. The parameters of these energy terms were fitted for a training set of 14 HIV-1 protease-inhibitor complexes of known 3D structure with a correlation coefficient of 0.91 and an unsigned mean error of 0.83 kcal/mol.",
author = "Zhang, {Da W.} and Huang, {Philip Lin} and Sylvia Lee-Huang and John Zhang",
year = "2008",
month = "8",
doi = "10.1142/S0219633608003915",
language = "English (US)",
volume = "7",
pages = "485--503",
journal = "Journal of Theoretical and Computational Chemistry",
issn = "0219-6336",
publisher = "World Scientific Publishing Co. Pte Ltd",
number = "4",

}

TY - JOUR

T1 - Design of hybrid inhibitors to HIV-1 protease

AU - Zhang, Da W.

AU - Huang, Philip Lin

AU - Lee-Huang, Sylvia

AU - Zhang, John

PY - 2008/8

Y1 - 2008/8

N2 - A series of HIV-1 protease (PR) inhibitors are designed to increase the binding affinity with PR subsites based on the quantum analysis of the contributions of molecular fragments in six FDA-approved PR drugs to the total binding interaction. The binding free energies were estimated by modified linear interaction energy approach [Zoete H, Michielin O, Karplus M, J Comput Aided Mol Des 17:861, 2003], in which the binding free energy is written as a linear combination of the electrostatic interaction energy between PR and the ligand, Eelec, the van der Waals interaction energy between PR and the ligand, EvdW, and the difference of the solvation free energies of the complex, the receptor and the isolated ligand, ΔGsolv. The parameters of these energy terms were fitted for a training set of 14 HIV-1 protease-inhibitor complexes of known 3D structure with a correlation coefficient of 0.91 and an unsigned mean error of 0.83 kcal/mol.

AB - A series of HIV-1 protease (PR) inhibitors are designed to increase the binding affinity with PR subsites based on the quantum analysis of the contributions of molecular fragments in six FDA-approved PR drugs to the total binding interaction. The binding free energies were estimated by modified linear interaction energy approach [Zoete H, Michielin O, Karplus M, J Comput Aided Mol Des 17:861, 2003], in which the binding free energy is written as a linear combination of the electrostatic interaction energy between PR and the ligand, Eelec, the van der Waals interaction energy between PR and the ligand, EvdW, and the difference of the solvation free energies of the complex, the receptor and the isolated ligand, ΔGsolv. The parameters of these energy terms were fitted for a training set of 14 HIV-1 protease-inhibitor complexes of known 3D structure with a correlation coefficient of 0.91 and an unsigned mean error of 0.83 kcal/mol.

UR - http://www.scopus.com/inward/record.url?scp=51449117426&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=51449117426&partnerID=8YFLogxK

U2 - 10.1142/S0219633608003915

DO - 10.1142/S0219633608003915

M3 - Article

AN - SCOPUS:51449117426

VL - 7

SP - 485

EP - 503

JO - Journal of Theoretical and Computational Chemistry

JF - Journal of Theoretical and Computational Chemistry

SN - 0219-6336

IS - 4

ER -