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Updated: May 15, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Treatment of Halogen Bonding in the OPLS-AA Force Field; Application to Potent Anti-HIV Agents
William L Jorgensen1, Patric Schyman
1Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107.
Abstract:
The representation of chlorine, bromine, and iodine in aryl halides has been modified in the OPLS-AA and OPLS/CM1A force fields in order to incorporate halogen bonding. The enhanced force fields, OPLS-AAx and OPLS/CM1Ax, have been tested in calculations on gas-phase complexes of halobenzenes with Lewis bases, and for free energies of hydration, densities, and heats of vaporization of halobenzenes. Comparisons with results of MP2/aug-cc-pVDZ(-PP) calculations for the complexes are included. Implementation in the MCPRO software also allowed computation of relative free energies of binding for a series of HIV reverse transcriptase inhibitors via Monte Carlo/free-energy perturbation calculations. The results support the notion that the activity of an unusually potent chloro analog likely benefits from halogen bonding with the carbonyl group of a proline residue.
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