Predicting agonism in GPCRs was presented by Dr Martin Slater, Cresset at the Cresset European User Group Meeting 2015.
The XED force field, developed by Dr Andy Vinter, is the foundation of all Cresset commercial field based software. Though the software is considered by many as ‘best in class’ for a number of ligand centric computational chemistry workflows, including scaffold hopping, virtual screening and bioisosteric fragment replacement, the XED force field is less well known for its wider utility in modeling larger molecular systems such as proteins. This is in spite of the fact that the Cresset consulting services team have continually used and developed this, over a decade, for both ligand and protein modeling work.
In order to highlight the finesse of the multipole force field, we have set ourselves an extreme challenge which, for some, represents the holy grail in GPCR research: the potential of predicting a pharmacological outcome. The latest GPCR structures have provided a unique opportunity to study the complete GPCR system incorporating both transmembrane protein and effector G-proteins. We have begun probing these systems and, with the resolution that the XED force field can provide, are beginning to glimpse the possibility of unravelling the effects of ligands on the energetics of G-protein binding in a quantitative manner.
See also Prediction of GPCR agonism.
