Molecular docking: The role of noncovalent interactions in the formation of protein-nucleotide and protein-peptide complexes

Knowledge of the spatial structure of complexes formed by cellular proteins and membrane receptors with their respective ligands is an important step towards understanding the mechanisms of their functioning. Rational drug design and the search for new therapeutically active compounds also require structural information on the interaction of prototypic drugs with the target protein. The present review briefly describes the main computational methods of molecular docking that are used to predict the conformation of a ligand bound to the active center of a protein. Approaches enabling an increase of the precision and efficiency of the currently used docking algorithms are exemplified by the recent projects of the Laboratory of Biomolecular Modeling of IBCh RAS. Special attention is paid to hydrophilic and hydrophobic interactions, as well as to the stacking phenomena that account for the molecular recognition of specific ligand fragments. These types of contacts are often inadequately described by the algorithms of the estimation of the intermolecular interaction energy of the existing docking programs (scoring functions), this ultimately leading to erroneous predictions of the three-dimensional structure of complexes. Therefore, a thorough consideration of these interactions is one of the most important tasks of molecular modeling.