Lead-Finder software can be used for extra precision calculations of the free energy
of protein-ligand binding. This functionality is quite unique to docking software,
since binding energy calculations are usually included in separate software packages that are
based on such theoretical approaches as free energy perturbation or linear interaction
energy. These packages require a high level of expertise in computational chemistry, and
are often time and investment intensive.
Thanks to the original semi-empiric molecular mechanical scoring function implemented
in Lead-Finder, extra precision calculations of the free energy of ligand-protein binding
can be performed on the flight with ligand docking. No extra computational/expert time
is required, and neither is any investment in additional software. The precision
of binding energy estimation with Lead-Finder was validated on a set
of 330 experimentally characterized protein-ligand complexes with a broad
distribution of ligand binding affinities and other physicochemical properties
(see Benchmarks section). This yielded a RMSD of 1.5 kcal/mol from experimental data.
Binding energy calculations can be performed concurrently with ligand docking, or for
a predetermined protein-ligand structure (obtained from experimental data or other molecular
modeling studies). Ability of Lead-Finder to accurately predict free energy of ligand binding
is hard to overestimate in drug discovery studies, modeling ADMET properties in silico,
studies of enzyme’s specificity and rational enzyme design.
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