By default, embedded docking inside Makya is done using Autodock Vina. The generated molecules are docked in the specified target protein binding pocket and optimized with respect to the Contact Score and the scoring function used by Autodock Vina, referred to as the Vina Score. We give here a brief overview of the Vina Score; for a more detailed description, the reader is invited to refer to the original Autodock Vina paper [1].
The conformation-dependent scoring function is predicted as the sum of distance-dependent interactions over all atom pairs excluding 1-4 interactions:
where d is the surface distance and h is a weighted sum of steric interactions, and where applicable, of hydrophobic interactions and hydrogen bonding. Hydrogen atoms are not included in the above equation.
The surface distance d can be computed as:
where r is the inter-atomic distance, and Ri and Rj the radii of atoms i and j.
The binding energy can be seen as the sum of intra- and inter-molecular contributions:
The predicted free energy of binding is a strictly increasing and smooth function (noted g) of the inter-molecular contribution of the lowest scoring conformation:
The free binding energy of other low-scoring conformations is a function of the scoring function associated with the conformation and of the intra-molecular contribution of the best binding mode:
As described in [1], "the derivation of the scoring function combines certain advantages of knowledge-based potentials and empirical scoring functions: it extracts empirical information from both the conformational preferences of the receptor-ligand complexes and the experimental affinity measurements".
References
- O. Trott, A. J. Olson, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading, Journal of Computational Chemistry 31 (2010) 455-461