1 South Asian J Exp Biol; 1 (S1): xxx‐xxx; 2011 ISSN: 2230‐9799 Vol. 1, Issue S1, Page xxx‐xxx http://www.sajeb.org REGULAR ARTICLE Virtual screening of natural bioactives in combating cancer through epigenetic modulation Ravi Kapopara* 1 , S. Prasanth Kumar 2 , Saumya K. Patel 1 , Dhananjay K. Sadhu 1 , Yogesh T. Jasrai 1 , Himanshu A. Pandya 1 and Rakesh M. Rawal 3 1 Bioinformatics Laboratory, Department of Botany, Gujarat University, Gujarat, India 2 Department of Bioinformatics, Alagappa University, Tamil Nadu, India 3 Division of Medicinal Chemistry and Pharmacogenomics, Department of Cancer Biology, The Gujarat Cancer and Research Institute (GCRI), Gujarat, India ARTICLE INFO Article History: Received: 20‐07‐2011 Revised: 27‐07‐2011 Accepted: 28‐07‐2011 *Corresponding Author: Email: ravi.kapopara@gmail.com Keywords: Epigenetics, Virtual screening, Natural bioactives, Ligand binding energy ABSTRACT Epigenetic events are due to altered gene expression without any changes in the genetic material and characteristic of heritability via cell division. The impact of epigenetic control over cancer is one among the thrust area of research in cancer biology. The present study deals about the virtual screen‐ ing of plant derived bioactives, directed against the key molecular regulators of the epigenetic events viz. DNA methyltransferases (DNMT1, DNMT2 and DNMT3B), Histone acetyltransferase (HAT), Histone deacetylase 8 (HDAC8), Histone H3 lysine 27 methyl transferase (H3K27MT) and Histone H3 specific lysine 4 demethylase (H3K4DM). This computational screening identifies the most efficient binders with respect to individual targets in terms of ligand binding energy. The structure optimization of the best scored docked confor‐ mations will be helpful to reveal new insights and development of natural bioactives to combat cancer. 1. Introduction Cancer is a term that encompasses a complex group of more than 100 different types of diseases associated with uncontrolled cell division. Epige‐ netic events are alterations in gene expression without changes in DNA sequence and characteris‐ tic of heritability via cell division. It is confidently anticipated that aberrant epigenetic control by chromatin modifying enzymes will be important for future therapy of human diseases including cancer (Egger et al., 2004). DNA methylation is a crucial mechanism associated with epigenetic regulation and it triggers chromatin reorganization. Genomic tumor DNA is generally characterized by distinct methylation changes also known as Epimutations. Hypomethylation at centromeric repeats se‐ quences has been linked to genomic instability (Ehrlich, 2002) whereas hypermethylation is ob‐ served in individual genes contributes to gene si‐ lencing. Histone specific acetylation, deacetylation and lysine specific methylation are the molecular events known to switch on/off the chromatin and thereby regulate gene expression (Grunstein, 1997, Khochbin et al., 2001). Epigenetic silencing is the main mechanism for in‐ activating repair genes. For example, the role of epigenetic silencing was studied in repair gene hMLH1 causing sporadic colon cancer. Methylation Special Issue on “Herbal immunomodulatory and therapeutic approaches against the infectious diseases" (Guest Editor: Dr. Lavkush Dwivedi, PhD)