The good, the bad and the twisted: a survey of ligand geometry in protein crystal structures

The protein databank now contains the structures of over 11,000 ligands bound to proteins. These structures are invaluable in applied areas such as structure-based drug design, but are also the substrate for understanding the energetics of intermolecular interactions with proteins. Despite their obvious importance, the careful analysis of ligands bound to protein structures lags behind the analysis of the protein structures themselves. We present an analysis of the geometry of ligands bound to proteins and highlight the role of small molecule crystal structures in enabling molecular modellers to critically evaluate a ligand model’s quality and investigate protein-induced strain

Supervised Molecular Dynamics (SuMD) Approaches in Drug Design

Supervised MD (SuMD) is a computational method that enables the exploration of ligand-receptor recognition pathway in a reduced timescale. The performance speedup is due to the incorporation of a tabu-like supervision algorithm on the ligand-receptor approaching distance into a classic molecular dynamics (MD) simulation. SuMD enables the investigation of ligand-receptor binding events independently from the starting position, chemical structure of the ligand (small molecules or peptides), and also from its receptor-binding affinity. The application of SuMD highlights an appreciable capability of the technique to reproduce the crystallographic structures of several ligand-protein complexes and can provide high-quality protein-ligand models of for which yet experimental confirmation of binding mode is not available