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Post Processing of Protein-Compound Docking for Fragment-Based Drug Discovery (FBDD): In-Silico Structure-Based Drug Screening and Ligand-Binding Pose Prediction

[ Vol. 10 , Issue. 6 ]


Yoshifumi Fukunishi   Pages 680 - 694 ( 15 )


For fragment-based drug development, both hit (active) compound prediction and docking-pose (protein-ligand complex structure) prediction of the hit compound are important, since chemical modification (fragment linking, fragment evolution) subsequent to the hit discovery must be performed based on the protein-ligand complex structure. However, the naive protein-compound docking calculation shows poor accuracy in terms of docking-pose prediction. Thus, postprocessing of the protein-compound docking is necessary. Recently, several methods for the post-processing of protein-compound docking have been proposed. In FBDD, the compounds are smaller than those for conventional drug screening. This makes it difficult to perform the protein-compound docking calculation. A method to avoid this problem has been reported. Protein-ligand binding free energy estimation is useful to reduce the procedures involved in the chemical modification of the hit fragment. Several prediction methods have been proposed for high-accuracy estimation of protein-ligand binding free energy. This paper summarizes the various computational methods proposed for docking-pose prediction and their usefulness in FBDD.


In-silico drug screening, protein-compound docking, virtual screening, Pharmacogram method, Consensus Ligand Binding mode Analysis method, Fragment Screening by Replica Generation, Smooth Reaction Path Generation, Filling potential


Biomedicinal Information Research Center (BIRC), National Institute of Advanced Industrial Science and Technology (AIST), 2-41-6, Aomi, Koto-ku, Tokyo 135-0064, Japan.

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