Tags: drugs molecular dynamics simulations Funnel-Metadynamics free energy calculations

the Funnel Metadynamics (FM) is a theoretical method proven to be very useful in obtaining an accurate estimation of the affinity between two molecules. This method decreases the overall simulation time by focusing the sampling to the binding states and the solvated one through the addition of a funnel-shaped potential, obtaining an efficient description of the binding free-energy surface and an accurate calculation of the absolute binding free-energy difference. It has been widely used to study ligand/protein interactions, but the full power of FM has not been completely exploited due to the lack of a friendly graphical user interface (GUI) and a thorough guide for the system set-up, which is of paramount importance to obtain a good result. Furthermore, FM could be adapted to tackle not only the ligand/protein interaction but also more challenging problems, such as the protein-protein interactions (PPI).
However, FM had been developed for the old package of Plumed 1.3, which has been partially abandoned after the release of the new version. The aim of this project is to present a new implementation of the FM for the new software Plumed 2 together with two tcl scripts for Visual Molecular Dynamics (VMD), very useful to set-up the Funnel potential and analyse the outcome of the simulation.
The implementation corrects some of the weaknesses of the previous method and the scripts come with a user-friendly interface, in order to be as easy as possible for all kind of users.

Prof. Dr. Vittorio Limongelli; ; PI; ICS

PhD Stefano Raniolo; ; ICS

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