2017/01/18 by Matthew Clark, Clark, Matthew, Jeffrey S. Wiseman +1
Biochemistry, Genetics and Molecular Biology · Materials Science · #82B80 #Biomolecules (q-bio.BM) #Chemical Physics (physics.chem-ph) #Enzyme Structure and Function #FOS: Biological sciences #FOS: Physical sciences #G.3 #I.6.8 #Photosynthetic Processes and Mechanisms #Protein Structure and Dynamics #Soft Condensed Matter (cond-mat.soft)
paper · pdf · doi:10.48550/arxiv.1701.05073
openalex publication_date 2017/01/18 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
The principles behind the computation of protein-ligand binding free energies by Monte Carlo integration are described in detail. The simulation provides gas-phase binding free energies that can be converted to aqueous energies by solvation corrections. The direct integration simulation has several characteristics beneficial to free-energy calculations. One is that the number of parameters that must be set for the simulation is small and can be determined objectively, making the outcome more deterministic, with respect to choice of input conditions, as compared to perturbation methods. Second, the simulation is free from assumptions about the starting pose or nature of the binding site. A final benefit is that binding free energies are a direct outcome of the simulation, and little processing is required to determine them. The well-studied T4 lysozyme experimental free energy data and crystal structures were used to evaluate the method.