Title:A Computational Investigation on Chitosan Derivatives using Pharmacophore-
based Screening, Molecular Docking, and Molecular Dynamics
Simulations against Kaposi Sarcoma
Volume: 20
Issue: 3
Author(s): Kiruba Sakthivel, Priyanka Ganapathy, Kirubhanand Chandrasekaran, Gowtham Kumar Subbaraj and Langeswaran Kulanthaivel*
Affiliation:
- Department of Biotechnology, Science Campus, Alagappa University, Karaikudi, Tamil Nadu, India
Keywords:
SOX (Shutoff Exonuclease), pharmacophore hypothesis, virtual screening, MM-GBSA, HOMO-LUMO, molecular docking and dynamic simulations.
Abstract:
Background: Cancer is one of the most dangerous illnesses to the human body due to
its severity and progressive nature. Kaposi's Sarcoma (KS) tumor can appear as painless purple
spots on the legs, foot, or face. This cancer develops in the lining of lymph arteries and blood vessels.
Along with the enlargement of lymph nodes, the vaginal region and the mouth portion are the
additional target areas of KS. DNA-binding proteins known as Sox proteins are found in all
mammals and belong to the HMG box superfamily. They controlled a wide range of developmental
procedures, such as the formation of the germ layer, the growth of organs, and the selection of
the cell type. Human developmental abnormalities and congenital illnesses are frequently caused
by the deletion or mutation of the Sox protein.
Aim: The purpose of this study is to determine the promising Kaposi's sarcoma inhibitors through
computational studies.
Objective: In this present study computational approaches were used to evaluate the anti- carcinogenic
efficacy against Kaposi's sarcoma.
Methods: Ligand-based pharmacophore screening was performed utilising four different chemical
libraries (Asinex, Chembridge, Specs, and NCI Natural products (NSC)) depending on the top
hypothesis. The top hits were examined using molecular docking, absorption, distribution, metabolism
and excretion. Highest occupied molecular orbital and lowest unoccupied molecular orbital
were analysed to determine the lead compounds' biological and pharmacological efficacy. The
results of the study indicated that the leading candidates were possible SOX protein inhibitors.
Results: A pharmacophore model to inhibit the production of SOX protein in Kaposi Sarcoma was
generated in this computational experiment using a set of 19 Chitosan compounds.
Conclusion: The results revealed that the top hits responded to all of the pharmacological druglikening
criteria and had the best interaction residues, fitness scores, and docking scores. The resulting
leads might be potential Kaposi's Sarcoma alternative treatments.
