Physical and Theoretical Chemistry

Computational Approaches to Drug and Molecular Design

Additional sessions will address physics-based binding free-energy methods, alchemical and endpoint techniques, and the treatment of protein flexibility, water networks, and entropic contributions to affinity. Presentations may cover structure-based and ligand-based design, fragment growing, de novo molecular generation, retrosynthetic feasibility scoring, and multi-objective optimization of potency against selectivity and pharmacokinetic behaviour. Discussion will extend to solvation models, protonation-state assignment, force-field quality for drug-like and covalent compounds, and benchmarking of scoring functions against curated experimental data. Uncertainty quantification, domain-of-applicability analysis, and prospective blind testing will also be considered as indicators of model reliability. Progress in computational methods for lead discovery and optimization will be welcomed, including hybrid workflows that combine docking or molecular dynamics with machine learning, quantum-chemical refinement, and experimental validation in cellular or biochemical assays.