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Volume 8 Journal of Clinical & Experimental Pharmacology Pharmacology and Medicinal Chemistry 2018
October 18-19, 2018
October 18-19, 2018 Dubai, UAE
International Conference on
18th International Conference on
&
Joint Meeting on
Pharmacology and Toxicology
Medicinal and Pharmaceutical Chemistry
Multiple crystal structure modeling in structure-based drug discovery: Case studies on successful
diverse lead identification
Yogeeswari Perumal
Birla Institute of Technology and Science, India
S tructure-based drug design has played significant role in the design of
various drug candidates. The most studied targets include the HIV protease,
dihydrofolate reductase, beta secretase etc. for which there are number of crystal
structures available in the protein databases (pdb). Our drug discovery research
group initiated the strategy of utilizing multiple crystal structures in the design
of diverse ligands of human beta secretase and was successful. In continuation to
our efforts in this field, we report here the discovery of diverse ligands for various
therapeutic classes utilizing structure-based design for those proteins where
more than hundred crystal structures were available in the pdb. We rationalized
the selection of crystal structures bound with different ligands based on the resolution of the structure, no mutation and
only the wild type. About nine to 10 crystal structures were employed in the structure-based drug design to develop energy-
based pharmacophore (e-pharmacophore) hypothesis based on the ligand interaction with the protein residues. Multiple
e-pharmacophores were generated and validated using enrichment factor calculation.The validated pharmacophore hypothesis
was utilized for filtering commercial database with pharmacophore fitness above 1.0. A high throughput screening combined
with docking, analysis of binding amino acid residues and ADME parameters led to the identification of some potential diverse
scaffolds that could be developed as novel inhibitors of HIV protease.
Recent Publications
1. JTPatrisha,DManvar, SKondepudi,MBBattu,DSriram,ABasu, PYogeeswari,NKBasu (2014)Multiple e-pharmacophore
modeling, 3D-QSAR and High-throughput virtual screening of Hepatitis C Virus NS5B polymerase Inhibitors. J. Chem.
Inf. Model; (ACS), 54: 539-552.
2. P Ravichand, D Sriram, P Yogeeswari, R Vadrevu (2013) Multiple E-Pharmacophore Modeling combined with High-
Throughput Virtual Screening and Docking to Identify Potential Inhibitors of Beta Secretase. Mol. Informatics; 32: 2-15.
Biography
Yogeeswari Perumal is currently working as a Professor and Associate Dean (Sponsored Research and Consultancy Division), Department of Pharmacy, Birla
Institute of Technology and Science, Pilani, Hyderabad Campus. She is the Founder of the Yogee’S Bioinnovations Pvt. Ltd, which is a drug discovery unit.
Yogeeswari Perumal, Clin Exp Pharmacol 2018, Volume 8
DOI: 10.4172/2161-1459-C3-034