Binding free energies for the SAMPL8 CB8 “Drugs of Abuse” challenge from umbrella sampling combined with Hamiltonian replica exchange

• Published in: Journal of computer-aided molecular design Vol. 36; no. 1; pp. 1 - 9
• Main Authors: Markthaler, Daniel, Kraus, Hamzeh, Hansen, Niels
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 2022; Springer Nature B.V
• Subjects: Affinity; Animal Anatomy; Binding; Bridged-Ring Compounds - chemistry; Chemistry; Chemistry and Materials Science; Computer Applications in Chemistry; Drugs; Empirical analysis; Energy; Free energy; Histology; Imidazoles - chemistry; Ligands; Molecular Dynamics Simulation; Morphology; Order parameters; Physical Chemistry; Protein Binding; Proteins - chemistry; Retrospective Studies; Sampling; Simulation; Systematic errors; Thermodynamics; Umbrella sampling; Host–guest complex; SAMPL8
• ISSN: 0920-654X; 1573-4951
• DOI: 10.1007/s10822-021-00439-w

Umbrella sampling along a one-dimensional order parameter in combination with Hamiltonian replica exchange was employed to calculate the binding free energy of five guest molecules with known affinity to cucurbit[8]uril. A simple empirical approach correcting for the overestimation of the affinity by the GAFF force field was proposed and subsequently applied to the seven guest molecules of the “Drugs of Abuse” SAMPL8 challenge. Compared to the uncorrected binding free energies, the systematic error decreased but quantitative agreement with experiment was only reached for a few compounds. From a retrospective analysis a weak point of the correction term was identified.