About this Research Topic
Structure-based virtual screening approaches that use molecular docking to generate models of enzyme-ligand interactions are now widely used in biochemistry, medicinal chemistry, drug discovery and development. This allows investigators to perform high throughput testing of large compound libraries (from hundreds to millions of individual molecules) and select the most promising molecules for experimental investigation. However, deficiencies of current scoring functions complicate ranking of docking poses and produce high “false positive” and “false negative” rates. Additional postdocking tools are therefore required to select the most promising ligands via accurate scoring/binding energy estimation, structural filtration, and prediction/assessment of physicochemical properties and activity spectra (including QSAR modeling).
This Research Topic will provide a forum to highlight important approaches for improving performance of virtual screening. For example, (i) some docking programs use additional scoring functions (along with dG-scoring) for correct rank-ordering of docked poses by assigning high scores to active ligands (true binders) than to inactive ones. (ii) The ability of ligands to form crucial interactions with a protein target, characteristic for the substrate and/or inhibitors, could be considered a structural criterion for identifying potent binders among docked compounds via structural filtration. The formation of specified interactions (hydrogen bonds, hydrophobic contacts, stacking, etc.) can be monitored for each docked ligand, and those ligands that meet the structural criteria are accepted, while the rest are rejected from further consideration. (iii) Some physicochemical properties of molecules (molecular weight, number of hydrogen bond donors/acceptors, Log P, pKa, etc.) as well as biological activities and adverse pharmacotherapeutic effects can be calculated/predicted and used to select candidates for further experimental investigations.
The scope will cover virtual screening studies using advanced docking and postdocking approaches aimed at the effective selection of active ligands with desired properties. Researchers are also encouraged to present results obtained from experimental validation of approaches used (for example, in vitro activity of selected compounds).
This Research Topic welcomes original articles and reviews focusing on, but not limited to, the following topics:
• Identification of small-molecule inhibitors/activators through molecular docking and virtual screening
• Using scoring function for correct rank-ordering of docked poses
• Using structural filtration for the selection of specifically bound ligands
• Selection of ligands with desired properties based on calculation of physicochemical parameters
• Prediction of biological activities and adverse effects (including QSAR modeling) for candidates selected by docking
• Development of new approaches to improving performance of virtual screening.
This Research Topic will provide a forum to highlight important approaches for improving performance of virtual screening. For example, (i) some docking programs use additional scoring functions (along with dG-scoring) for correct rank-ordering of docked poses by assigning high scores to active ligands (true binders) than to inactive ones. (ii) The ability of ligands to form crucial interactions with a protein target, characteristic for the substrate and/or inhibitors, could be considered a structural criterion for identifying potent binders among docked compounds via structural filtration. The formation of specified interactions (hydrogen bonds, hydrophobic contacts, stacking, etc.) can be monitored for each docked ligand, and those ligands that meet the structural criteria are accepted, while the rest are rejected from further consideration. (iii) Some physicochemical properties of molecules (molecular weight, number of hydrogen bond donors/acceptors, Log P, pKa, etc.) as well as biological activities and adverse pharmacotherapeutic effects can be calculated/predicted and used to select candidates for further experimental investigations.
The scope will cover virtual screening studies using advanced docking and postdocking approaches aimed at the effective selection of active ligands with desired properties. Researchers are also encouraged to present results obtained from experimental validation of approaches used (for example, in vitro activity of selected compounds).
This Research Topic welcomes original articles and reviews focusing on, but not limited to, the following topics:
• Identification of small-molecule inhibitors/activators through molecular docking and virtual screening
• Using scoring function for correct rank-ordering of docked poses
• Using structural filtration for the selection of specifically bound ligands
• Selection of ligands with desired properties based on calculation of physicochemical parameters
• Prediction of biological activities and adverse effects (including QSAR modeling) for candidates selected by docking
• Development of new approaches to improving performance of virtual screening.
Keywords: virtual screening, docking, scoring function, structural filtration, molecular modeling, QSAR
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
