Design of hybrid inhibitors to HIV-1 protease

Da W. Zhang; Philip Lin Huang; Sylvia Lee-Huang; John Z.H. Zhang

doi:10.1142/S0219633608003915

Design of hybrid inhibitors to HIV-1 protease

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

Chemistry

Research output: Contribution to journal › Article › peer-review

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, E_elec, the van der Waals interaction energy between PR and the ligand, E_vdW, and the difference of the solvation free energies of the complex, the receptor and the isolated ligand, ΔG_solv. 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 language	English (US)
Pages (from-to)	485-503
Number of pages	19
Journal	Journal of Theoretical and Computational Chemistry
Volume	7
Issue number	4
DOIs	https://doi.org/10.1142/S0219633608003915
State	Published - Aug 2008

ASJC Scopus subject areas

Computer Science Applications
Physical and Theoretical Chemistry
Computational Theory and Mathematics

Access to Document

10.1142/S0219633608003915

Cite this

@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 Zhang, {John Z.H.}",

year = "2008",

month = aug,

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 Z.H.

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

SN - 0219-6336

VL - 7

SP - 485

EP - 503

JO - Journal of Theoretical and Computational Chemistry

JF - Journal of Theoretical and Computational Chemistry

IS - 4

ER -

Design of hybrid inhibitors to HIV-1 protease

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this