Identification of ZAP-70 Inhibitor from Macroalgae through Docking and Molecular Dynamics Studies
Jayasurya Selva Sekar, Keerthi Kesavan, Rambabu Majji, Jayanthi Sivaraman*
Computational Drug Design Lab, Department of Biotechnology, School of Bio Sciences and Technology, VIT University, Vellore, 632014, Tamil Nadu, India
*Corresponding Author E-mail: firstname.lastname@example.org
Online published on 26 March, 2018.
Leukemia is a cancer of the blood when there is abnormality in the proliferation of White blood cells. Chronic lymphocytic leukemia (CLL) is caused when there is an abnormal growth of B cells in the bone marrow and lymph nodes. By identifying the unique biomarkers associated with CLL we can find better targeted therapies. Cell survival signalling protein ZAP-70 (Zeta-chain-associated protein kinase 70) is aunique prognostic biomarker present only in the CLL B cells and absent in normal B cells and so it is a potent therapeutic target. Through molecular docking methods we can find novel compounds to inhibit ZAP-70. Seaweeds has many therapeutic properties are considered as medicines. Their exploitation in the medical scenario has been ever increasing. The Algae possesses a high number of metabolites with anticancer properties and so compounds from seaweeds can be potential inhibitors for ZAP-70. In this study, seaweed compounds were docked against ZAP-70 using GLIDE module. The molecular docking results revealed that aseaweed compound, Methyl N, N'bis-(2, 3-dibromo-4, 5-dihydroxybenz-yl)-y-ureidobutryate (RR017) showed highest binding to ZAP-70 kinase domain. Thereby inhibiting the signalling to B cell receptor required for the survival of the cancer cells. Computational studies enable us to find inhibitors and analyse binding interactions of ligand to protein. The study indicated that the algae compound RR017 can be used as a potent therapeutic ligand for CLL treatment.
Chronic lymphocytic leukaemia, Seaweed metabolites, ZAP-70, Docking, GLIDE.