Computational Calorimetry: High-Precision Calculation of Host-Guest Binding Thermodynamics.

ABSTRACT: We present a strategy for carrying out high-precision calculations of binding free energy and binding enthalpy values from molecular dynamics simulations with explicit solvent. The approach is used to calculate the thermodynamic profiles for binding of nine small molecule guests to either the cucurbit[7]uril (CB7) or β-cyclodextrin (βCD) host. For these systems, calculations using commodity hardware can yield binding free energy and binding enthalpy values with a precision of ∼0.5 kcal/mol (95% CI) in a matter of days. Crucially, the self-consistency of the approach is established by calculating the binding enthalpy directly, via end point potential energy calculations, and indirectly, via the temperature dependence of the binding free energy, i.e., by the van't Hoff equation. Excellent ag

SUBMITTER: Henriksen NM 

PROVIDER: S-EPMC4614838 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature