Funnel-Metadynamics (FM)

Overview

FM is a combination of Metadynamics bias potential [78] with a funnel-shape restraint potential applied to the target structure of a binding interaction. The latter is composed of a cone restraint, which covers the ligand binding site, and a cylindrical one that heads towards the solvent [83]. When inside the funnel volume, the ligand does not feel any restraint potential, proceeding as regular Metadynamics. Upon reaching the boundaries of the funnel, a repulsive bias is applied forcing the ligand to remain in the allowed funnel space. The result is an acceleration in the sampling of the binding/unbinding process, leading to a swift convergence of the calculation and a well-defined binding free-energy surface.

Installation

This module is not installed by default. Add '--enable-modules=funnel' to your './configure' command when building PLUMED to enable these features.

Usage

This module is a direct evolution of the original FM [83] since it incorporates an alignment function that removes the necessity to block the target macromolecule in the simulation box.

The user can follow a comprehensive protocol [114], which will help in all stages of the simulation, including pre- and post-processing. An example of input file can be found on FUNNEL-NEST's webpage

Module Contents

The funnel module is composed of a collective variable that calculates the position of a ligand with respect to a line and a potential that creates a funnel-shape restraint centered on the line (FUNNEL_PS and FUNNEL, respectively).