Binding Thermodynamics of Host-Guest Systems with SMIRNOFF99Frosst 1.0.5 from the Open Force Field Initiative.

ABSTRACT: Designing ligands that bind their target biomolecules with high affinity and specificity is a key step in small-molecule drug discovery, but accurately predicting protein-ligand binding free energies remains challenging. Key sources of errors in the calculations include inadequate sampling of conformational space, ambiguous protonation states, and errors in force fields. Noncovalent complexes between a host molecule with a binding cavity and a druglike guest molecule have emerged as powerful model systems. As model systems, host-guest complexes reduce many of the errors in more complex protein-ligand binding systems, as their small size greatly facilitates conformational sampling, and one can choose systems that avoid ambiguities in protonation states. These features, combined with their e

SUBMITTER: Slochower DR 

PROVIDER: S-EPMC7328435 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature