A swift all-atom energy-based computational protocol to predict DNA-ligand binding affinity and ΔTm

A hybrid molecular mechanics-statistical mechanics-solvent accessibility-based computational protocol is developed to calculate DNA-ligand binding affinity without any database training and is validated on 50 DNA-ligand complexes. The calculated binding energies yield high correlation coefficients of 0.95 (R(2) = 0.90) and 0.96 (R(2) = 0.93) in linear plots against experimental binding free energies (Delta G(o)) and Delta T(m), respectively. The protocol is translated into a swift, web-enabled, freely accessible computational tool, http://www.scfbio-iitd.res.in/preddicta, for Delta G(o) and Delta T(m) prediction for DNA-ligand complexes to aid and expedite rational drug design attempts.