Fragment based drug design (FBDD) is a structure guided ligand design approach used in
the process of drug discovery. It involves identification of low molecular weight fragments as hits followed
by determination of their binding mode using X-ray crystallography and/or NMR spectroscopy.
X-ray protein crystallography is one of the most sensitive biophysical methods used for screening and
is least prone to false positives. It also provides detailed structural information of the protein–fragment
complex at the atomic level. The retrieved binding information facilitates the optimization of fragments
into drug like molecules. These identified molecules bind efficiently with the target proteins and form
high quality binding interactions. Fragment-based screening using X-ray crystallography is, therefore,
an efficient method for identifying binding hotspots on proteins that can be further exploited by chemists
and biologists for the discovery of new drugs. The recent advancements in FBDD technique are
illustrated in this review along with recently published success stories of FBDD technique in drug discovery.
Keywords: Drug discovery, FBDD, NMR, X-ray crystallography, CADD, HTS.
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