ABSOLUTE BINDING FREE ENERGY PERTURBATION METHOD FOR PREDICTING DRUG TARGET BINDING STRENGTH

摘要

An absolute binding free energy perturbation method for predicting the drug target binding strength, comprising: on the basis of the fitting of the probability distribution of a constraint probability distribution function to a process of adding constraints, fitting the probability distribution to the remaining windows by using a linear combination of a plurality of Gaussian functions for the probability distribution obtained by counting windows of the remaining thermodynamic cycle steps, regenerating a potential difference according to the fit probability distribution, and finally counting to obtain the absolute binding free energy of a drug target. By fitting the probability distribution corresponding to the dynamics simulation trajectory in the intermediate state of the free energy perturbation, the probability distribution of sampling is more reasonable, and the convergence and accuracy of the energy calculation result are greatly improved.