Small-molecule drug discovery involves the optimization of various physicochemical
properties of a ligand, particularly its binding affinity for its target receptor (or receptors). In …

Noncovalent binding provides an invisible wiring diagram for biomolecular pathways and is
the essence of host-guest and supramolecular chemistry. Decades of theoretical and …

Rational drug design is predicated on knowledge of the three-dimensional structure of the
protein− ligand complex and the thermodynamics of ligand binding. Despite the …

Biologically relevant macromolecules, such as proteins, do not operate as static, isolated
entities. On the contrary, they are involved in numerous interactions with other species, such …

In this study, we introduce a fast and reliable rescoring scheme for docked complexes based
on a semiempirical quantum mechanical PM6-DH2 method. The method utilizes a PM6 …

Predicting protein-binding affinities of small molecules, even closely related ones, is a
formidable challenge in biomolecular recognition and medicinal chemistry. A …

Configurational entropy is thought to influence biomolecular processes, but there are still
many open questions about this quantity, including its magnitude, its relationship to …

For several drug leads obtained by tethering weak binding ligands, the dissociation constant
is smaller than the product of those of the individual fragments by a factor named the linking …

Isothermal titration calorimetry (ITC) is a fast, accurate and label‐free method for measuring
the thermodynamics and binding affinities of molecular associations in solution. Because the …

Water molecules can be found interacting with the surface and within cavities in proteins.
However, water exchange between bulk and buried hydration sites can be slow compared …