Computer-based techniques for lead identification and optimization II: Advanced search methods

This paper focuses on advanced computational techniques for identifying and optimizing lead molecules, such as metadynamics and a novel dynamic 3D pharmacophore analysis method called Dynophores. In this paper, the first application of the funnel metadynamics of the Berberine binding to G-quadruplex DNA is depicted, disclosing hints for drug design, in particular clarifying water’s role and suggesting the design of derivatives able to replace the solvent-mediated interactions between ligand and DNA to achieve more potent and selective activity. Secondly, the novel dynamic pharmacophore approach is an extension of the classic 3D pharmacophores, with statistical and sequential information about the conformational flexibility of a molecular system derived from molecular dynamics (MD) simulations.