There has typically been a divide between tools for three-dimensional (3D) structure-based design and those for analysis of structure-activity relationships (SAR) based on two-dimensional (2D) compound structures. Seamless integration between these approaches would enable all the available structural knowledge to be used to guide the efficient design of high quality, active compounds. We have been working together with BioSolveIT to seamlessly integrate their unique SeeSAR™ technology, including pose generation, HYDE scoring and torsion angle analysis within our StarDrop™ platform. In this webinar, we will illustrate how 2D analyses of SAR, such as activity cliff detection and matched molecular pair analyses, can be seamlessly linked in a highly visual way with related 3D structural information to understand and rationalize this SAR. Furthermore, information from 2D models of key physicochemical and absorption, distribution, metabolism, elimination and toxicity (ADMET) properties can be combined with 3D docked poses and affinity estimates. The influence of each atom or functional group on these properties can be highlighted and combined with visualization of the atomistic contributions to binding affinity, enabling development of optimization strategies that balance potency with the ADMET properties required in a safe and efficacious drug.
These combined capabilities enable the efficient design of compounds with improved target affinity in a truly multi-parameter optimization environment.
guest speaker: Dr. Matthew Segall, CEO at Optibrium Ltd, Cambridge, United Kingdom
0 Comments