Bioactive molecules of natural origin are a key resource for drug development.
Phytochemicals are gaining increasing attention due to promising results in studies on
cancer and neurodegenerative diseases. They often exhibit polypharmacological
activity, which can have both positive and negative effects, making them important to
study. However, classical experimental methods are inefficient for the required large
scale studies, which need better solutions, such as computer-aided drug design. These
approaches are divided into ligand-based and structure-based, with inverse docking
being the most suitable for identifying molecular targets. However, there is currently no
web-accessible tool that allows inverse docking of molecules to large databases of
binding sites. Therefore, we have developed a web server, publicly available on
http://probis-dock-server.insilab.org/, which uses the ProBiS-Dock algorithm together
with the ProBiS-Dock (220,760 proteins) and ProBis-Fold (all human proteins) binding
sites databases. The server accepts a molecule file, allows database selection and
docking parameter customization, performs docking, and returns results in an accessible
format. As a use case, we conducted the first large-scale inverse docking study of the
molecule alpha-cyperone, which is used in traditional medicine for various human
diseases. We listed the top 100 predicted targets in a table and performed a KEGG
PATHWAY enrichment analysis with them. We found 142 enriched biological
pathways, 35 of which were associated with Alzheimer’s disease. The results of our
study and the limited research on alpha-cyperone indicate the importance of further
investigation of this molecule. The targets we predicted serve as a basis for further
studies to understand its molecular interactions and therapeutic potential in
neurodegenerative diseases.
