Identification of Novel Molecular Scaffolds as Inhibitors of SP2 Protein - An Insilico Approach
Posted: 5 Feb 2020
Date Written: February 1, 2020
Abstract
Human body is made up of small basic units called cells. The systematic process of growth by division to make new cells and death of old or damaged cells is carried out in every human body. But if the systematic process is interfered by the genetic changes in the cells, causes Cancer. The present targeted protein (SP2) is one of the subgroup of Serine Proteases family consisting of 15 homologous peptidases. Protein SP2 is responsible for the most common, Prostate cancer in males (19% of total population) and an estimated cancer deaths in 2018 was about 9% in US. Prostate specific antigen (PSA) of present protein is most useful tumor marker for prostate cancer screening, diagnosis, prognosis and monitoring.
The discovery of new scaffolds for the present targeted protein can be approached by Insilico techniques like Homology modelling and Structure based drug designing. New Scaffold molecules with high affinity, specificity, activity, with less side effects and less toxicity values than the existing molecules can be identified by applying the Insilico techniques. The 3D model of SP2 protein was generated by homology modelling technique using Modeller 9.20. The generated protein structure of SP2 has 4α- helices, 3β-sheets and 1 gamma turn. A grid was generated at the active site region and virtual screening was carried out using Schrödinger Virtual Screening workflow. The virtual screening results show that HIS94, ASP142 and SER235 residues in SP2 protein are essential for binding with the ligand molecules. These molecular scaffolds with satisfactory ADME properties were identified as potential lead molecules against SP2 protein.
Keywords: Serine Proteases, Cancer, Homology modelling, Drug designing & Virtual Screening
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