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On Analytical Corrections for Restraints in Absolute Binding Free Energy Calculations

Stefan Boresch

2024Journal of Chemical Information and Modeling12 citationsDOIOpen Access PDF

Abstract

Double decoupling absolute binding free energy simulations require an intermediate state at which the ligand is held solely by restraints in a position and orientation resembling the bound state. One possible choice consists of one distance, two angle, and three dihedral angle restraints. Here, I demonstrate that in practically all cases the analytical correction derived under the rigid rotator harmonic oscillator approximation is sufficient to account for the free energy of the restraints.

Topics & Concepts

Dihedral angleDecoupling (probability)Position (finance)Harmonic oscillatorPhysicsEnergy (signal processing)Classical mechanicsChemistryQuantum mechanicsMoleculeEngineeringControl engineeringEconomicsHydrogen bondFinanceAdvanced Chemical Physics StudiesProtein Structure and DynamicsSpectroscopy and Quantum Chemical Studies
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