Molecular Mechanics/Coarse-Grained Models

Molecular simulations have proved to be extremely successful in predicting structures and energetics of ligand binding to their target receptors. However standard approaches are challenged when one has to deal with homology models based on templates with low sequence identity. In an effort at facing this challenge we have developed a hybrid molecular mechanics/coarse-grained (MM/CG) simulations approach, aimed at connecting the disparate spatial and temporal scales relevant to complex biological processes. This approach concentrates the efforts in characterizing the binding cavity while renouncing to most of protein details which are likely to be predicted in a rather inaccurate way by bioinformatics techniques. Examples of application of this technique to GPCRs illustrate the power of this approach