FMdb - FMdb: the database to perform funnel-metadynamics calculations on GPCR systems

Funnel-metadynamics (FM) is a powerful technique that allows elucidating the binding mode and mechanism of a ligand to its molecular target, also accurately estimating the binding free energy. FM was developed and improved by our research group. Our technique has been successfully employed to study many ligand/protein systems, however its broad use is limited by the complexity of the simulation setup.

In this project, we aim at creating a new open-access database of ready-to-use FM inputs, named FMdb, focused on ligand binding to G protein-coupled receptors (GPCRs). GPCRs are transmembrane proteins involved in conducting extracellular signals into the cell environment. These receptors play a pivotal role in various physiological and pathological processes, representing a most relevant pharmaceutical target. The functional mechanism of GPCRs can be controlled by orthosteric or allosteric ligands that can trigger GPCRs transition towards active or inactive states. GPCRs complexes can be classified depending on the ligand binding mode at extracellular, intra-membrane and intracellular level. 

In the present project, we will create a database of FM input files useful to perform binding free energy calculations at the orthosteric and allosteric binding sites for all the experimentally resolved GPCR structures. The developed database will support the community by providing ready-to-use FM inputs and stimulate the implementation of FM in drug discovery studies.