HybridDock: A Hybrid Protein–Ligand Docking
Protocol Integrating Protein- and Ligand-Based Approaches
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Abstract
Structure-based
molecular docking and ligand-based similarity search
are two commonly used computational methods in computer-aided drug
design. Structure-based docking tries to utilize the structural information
on a drug target like protein, and ligand-based screening takes advantage
of the information on known ligands for a target. Given their different
advantages, it would be desirable to use both protein- and ligand-based
approaches in drug discovery when information for both the protein
and known ligands is available. Here, we have presented a general
hybrid docking protocol, referred to as HybridDock, to utilize both
the protein structures and known ligands by combining the molecular
docking program MDock and the ligand-based similarity search method
SHAFTS, and evaluated our hybrid docking protocol on the CSAR 2013
and 2014 exercises. The results showed that overall our hybrid docking
protocol significantly improved the performance in both binding affinity
and binding mode predictions, compared to the sole MDock program.
The efficacy of the hybrid docking protocol was further confirmed
using the combination of DOCK and SHAFTS, suggesting an alternative
docking approach for modern drug design/discovery