Supercomputer docking with a large number of degrees of freedom

ABSTRACT

Docking represents one of the most popular computational approaches in drug design. It has reached popularity owing to capability of identifying correct conformations of a ligand within an active site of the target-protein and of estimating the binding affinity of a ligand that is immensely helpful in prediction of compound activity. Despite many success stories, there are challenges, in particular, handling with a large number of degrees of freedom in solving the docking problem. Here, we show that SOL-P, the docking program based on the new Tensor Train algorithm, is capable to dock successfully oligopeptides having up to 25 torsions. To make the study comparative we have performed docking of the same oligopeptides with the SOL program which uses the same force field as that utilized by SOL-P and has common features of many docking programs: the genetic algorithm of the global optimization and the grid approximation. SOL has managed to dock only one oligopeptide. Moreover, we present the results of docking with SOL-P ligands into proteins with moveable atoms. Relying on visual observations we have determined the common protein atom groups displaced after docking which seem to be crucial for successful prediction of experimental conformations of ligands.

KEYWORDS:

• Molecular modelling
• docking
• tensor train
• protein moveable atoms
• drug design

Acknowledgements

The work was financially supported by the Russian Science Foundation, Agreement no. 15-11-00025-П. The research is carried out using the equipment of the shared research facilities of HPC computing resources at Lomonosov Moscow State University, including the Lomonosov supercomputer [36].

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Russian Science Foundation [15-11-00025-П].