Design of hybrid inhibitors to HIV-1 protease

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

Research output: Contribution to journalArticlepeer-review


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
Issue number4
StatePublished - Aug 2008

ASJC Scopus subject areas

  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Computational Theory and Mathematics


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