“Ligand strain” is how we think of the energy cost for the ligand to adopt the bioactive conformation. Unfortunately, most modelers have historically thought of this from an “enthalpy-only” perspective, in terms of the relative energy of the ligand’s bioactive conformation compared to the global energy minimum. This has left out important entropy components, such as ligand flexibility, that we know affect the free energy of the unbound ligand. FreeForm uses a fast and easy workflow to calculate the free energy cost of forming the bioactive conformation, explicitly including entropy terms such as ligand flexibility. This computed conformer free energy serves as a substantially improved estimate of ligand strain.
In this webinar we will cover:
Conformer free energies within the unbound ligand ensemble
How strain energy and ligand entropy relate to conformer free energy
Constraining the ligand: can we know if it will improve potency?