| 摘要 |
A novel method for the determination of the binding free energy between a host or receptor molecule and a ligand substance is disclosed. The method comprises the determination of adjusted combinations of the average energy difference between the contribution from a) polar and b) non-polar interactions between the substance in two states, one where the substance alone and another where the substance bound to the host or receptor molecule is surrounded by solvent. The contributions from the polar and non-polar interactions are preferably provided by molecular dynamics simulations derived from 3-dimensional representations of the receptor molecule and the substance. The method renders possible the computation of binding free energies without the use of Monte Carlo simulations/free energy perturbation techniques and thus requires less computational resources than known methods. Also disclosed are methods for selecting/providing substances capable of interacting with a host or receptor molecule. |
