The Impact of Software Used and the Type of Target Protein on Molecular Docking Accuracy

The modern development of computer technology and different in silico methods have had an increasing impact on the discovery and development of new drugs. Different molecular docking techniques most widely used in silico methods in drug discovery. Currently, the time and financial costs for the initial hit identification can be significantly reduced due to the ability to perform high-throughput virtual screening of large compound libraries in a short time. However, the selection of potential hit compounds still remains more of a random process, because there is still no consensus on what the binding energy and ligand efficiency (LE) of a potentially active compound should be. In the best cases, only 20–30% of compounds identified by molecular docking are active in biological tests. In this work, we evaluated the impact of the docking software used as well as the type of the target protein on the molecular docking results and their accuracy using an example of the three most popular programs and five target proteins related to neurodegenerative diseases. In addition, we attempted to determine the “reliable range” of the binding energy and LE that would allow selecting compounds with biological activity in the desired concentration range.