Molecular Docking Using Quantum Mechanical-based Methods

AUCAR, MARÍA G.; CAVASOTTO, CLAUDIO N.

METHODS IN MOLECULAR BIOLOGY (CLIFTON, N.J.)

Springer Nature

Año: 2020 vol. 2114 p. 269 - 284

1064-3745

Computational methodsare a powerful and consolidated tool in the early stage of the drug leaddiscovery process. Among them, high-throughput molecular docking has proved tobe extremely useful in identifying novel bioactive compounds within large chemicallibraries. In the docking procedure, the predominant binding mode of eachsmall-molecule within a target binding site is assessed, and a docking scorereflective of the likelihood of binding is assigned to them. These methods alsoshed light on how a given hit could be modified in order to improve protein-ligandinteractions, and are thus able to guide lead optimization. The possibility toreducing time and cost compared to experimental approaches made this technologyhighly appealing. Due to methodological developments and the increase ofcomputational power, the application of quantum mechanical methods to studymacromolecular systems has gained substantial attention in the last decade. A quantummechanical description of the interactions involved in molecular association ofbio-molecules may lead to better accuracy compared to molecular mechanics,since there are many physical phenomena that cannot be correctly described withclassical approximations, such as covalent bond formation, polarizationeffects, charge transfer, bond rearrangements, halogen bonding, and others thatrequire electrons to be explicitly accounted for.  Considering the fact that quantum mechanics-basedapproaches in biomolecular simulation constitute an active and important fieldof research, we highlight in this work the recent developments of quantummechanical-based molecular docking and high-throughput docking.