Empirical Energy Functions for Molecular Docking

In the
DivCon Discovery Suite v.DEV.671-b4608, we provide two empirical energy
functions: the GARF statistical potential^{70 (link)} and the AMBERff14 functional potential^{63 (link),71 (link)} optimized for the MT method. The holo-protein:ligand complex binding
modes can be either generated using the “built-in” MT_Dock protein:ligand docking module^{55 (link)} or provided from other sources such as molecular simulations or
alternative protein:ligand docking protocols. In order to compare
the MT protocol performances with different settings, we applied both
the GARF potential function and the AMBERff14 force field for the
partition function calculation, and we used both MT_Dock and the industry-standard Molecular Operating Environment (MOE)
v.2019.0102 from Chemical Computing Group, Inc. to generate contrasting
protein:ligand complex poses. For MT_Dock and optionally
for the MOE interface (in the “three-step workflow”
discussed below), ligand conformers were generated using MT_CS.^{59 (link)} The MT_CS method was used
in all cases to calculate the unbound partition function. Figure 4 depicts a flowchart to aid in understanding
how the various MT parts work together (and with third-party methods)
to complete and generate the MT scores.