Predicting the gas chromatographic retention indices (RIs) of sulphur-containing polycyclic aromatic hydrocarbons (S-PAHs) is challenging due to positional isomerism, which introduces subtle structural variations that are not well captured by conventional physicochemical descriptors or simple partitioning models. In this study, a quantitative structure-retention relationship (QSRR) model was developed to accurately predict the RIs of S-PAHs using three molecular descriptors calculated with AlvaDesc software. Among the evaluated variables, solvation-weighted connectivity indices (X3sol, X4sol, and X5sol) emerged as the most influential descriptors governing chromatographic behaviour and selectivity. The model was built using a training set of 35 compounds and externally validated with an independent test set of 13 compounds. It demonstrated excellent predictive performance, with an adjusted coefficient of determination (R2adj.) of approximately 0.99 for both datasets. Residual analysis confirmed the robustness of the model, showing deviations mostly within +/- 5 RI units and no systematic error. Overall, solvation-weighted connectivity indices effectively capture subtle topological differences among positional isomers, providing a robust, interpretable, and reliable framework for predicting and understanding the retention behaviour of S-PAHs.
Herpes simplex virus type 1 (HSV-1) is highly prevalent, but emerging drug-resistant strains against nucleoside analogs like acyclovir demand novel therapeutics. This study employed an in silico drug repurposing approach to screen 41 beta-blockers as potential non-nucleoside inhibitors targeting HSV-1 thymidine kinase (TK). Molecular docking, 100 ns molecular dynamics (MD) simulations, MM/GBSA binding free energy calculations, per-residue energy decomposition, and ADMET analysis were performed. Docking results revealed several beta-blockers surpassed acyclovir (-5.20 kcal/mol) in binding energy, with bopindolol emerging as the top candidate (-9.32 kcal/mol). Interaction analysis showed bopindolol forms stable hydrogen bonds with Gln125, Arg163, and Arg222, alongside stabilizing hydrophobic interactions. MD simulations confirmed the structural stability of the bopindolol-HSV-1 TK complex, evidenced by stable RMSD, low residue fluctuations, persistent hydrogen bonding, and consistent protein compactness. MM/GBSA calculations yielded a favourable delta G binding of -53.08 +/- 3.57 kcal/mol. Energy decomposition indicated binding is driven by van der Waals and electrostatic interactions, with key contributions from Arg222, Tyr172, Met128, and Gln125. Furthermore, ADMET analysis demonstrated favourable pharmacokinetic properties for bopindolol. Overall, bopindolol represents a promising non-nucleoside inhibitor scaffold targeting HSV-1 TK, warranting further experimental validation.
