Selection of a molecule that specifically targets the cell-surface Human Epidermal growth factor Receptor 2: in silico docking simulation

Abstract

[Excerpt] Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% of the total cancer cases and 14% of the cancer deaths.1 Human Epidermal growth factor Receptor 2 (HER2) is a protein that is overexpressed in 25-30% of breast cancers and is involved in cell growth regulation, survival and differentiation.2 Aptamers generated from Systematic Evolution of Ligands by EXponential Enrichment (SELEX) emerged as a potential new tool for the development of targeted cancer therapies due to their three-dimensional structures that specifically recognize cell surface receptors, such as HER2.3 In this study, HER2-aptamers were screened and identified using SELEX. To design an approach for computational analysis of the isolated aptamers, their structures were modelled by mfold4, a web-based methodology for DNA structure prediction and hybridization software. The HER2 protein structure was obtained from Protein Data Bank (PDB) and using ZDOCK server5, the aptamer-target interactions were predicted through a combination of shape complementarity and statistical potential terms for scoring. [...]