CYCLE CLOSURE ESTIMATION OF RELATIVE BINDING AFFINITIES AND ERRORS

摘要

Methods for assessing the consistency and reliability of the calculations using cycle closures in relative binding free energy calculation paths. The methods are used for determining relative strength of binding between a receptor and individual members of a set ligands to form complexes between individual ligand set members and the receptor, in which the binding free energy difference with the lowest error is determined by probabilistic determination of the free energy differences and error distributions about those differences along each of the legs of the closed thermodynamic cycle that probabilistically lead to the hysteresis(es) value(s) observed for each closed of the closed thermodynamic cycle.