The past 20 years have seen many advances in our understanding of protein-protein
interactions (PPIs) and how to target them with small-molecule therapeutics. In 2004, we …

Docking is now routine in virtual screening or lead optimization for drug screening and
design. The number of papers related to docking has dramatically increased over the past …

Somatic mutations in the small GTPase K-Ras are the most common activating lesions found
in human cancer, and are generally associated with poor response to standard therapies …

Allostery is largely associated with conformational and functional transitions in individual
proteins. This concept can be extended to consider the impact of conformational …

Many human malignancies are associated with aberrant regulation of protein or lipid
kinases due to mutations, chromosomal rearrangements and/or gene amplification. Protein …

Appropriate tuning of binding selectivity is a primary objective in the discovery and
optimization of a compound on the path toward developing a drug. The environment in …

The question of how allostery works was posed almost 50 years ago. Since then it has been
the focus of much effort. This is for two reasons: first, the intellectual curiosity of basic science …

Many proteins have small-molecule binding pockets that are not easily detectable in the
ligand-free structures. These cryptic sites require a conformational change to become …

Cryptic allosteric sites—transient pockets in a folded protein that are invisible to
conventional experiments but can alter enzymatic activity via allosteric communication with …

The discovery of drug-like molecules that bind pockets in proteins that are not present in
crystallographic structures yet exert allosteric control over activity has generated great …