Understanding DNA Cleavage with Organometallic Molecules
Abstract
The goal of this ROPO project is to understand how different natural and non-natural materials bind to DNA and induce either single strand or full double strand cleavage. The approach to accomplishing the goal involves computing the molecular recognition of known biological materials, like bleomycins, for specific DNA sequences. Bleomycins (BLMs) were first isolated over forty years ago and constitute a family of structurally related glycopeptide-derived natural products with clinical antitumor activity. Metal-complexed bleomycins like DNA-bound Co(III)~BLM B2 cleave at preferred 5~-GT cleavage sites so we will examine this and related (simpler) systems to probe the controlling forces that determine major vs minor groove binding, head-to-head vs head-to-tail orientations, specific inter-molecular interactions giving rise to the molecular recognition, and controllable external influences like salt concentrations, temperatures, etc. Via MD simulations using the AMBER99 force field this study will be done computationally and assessed. The result will allow us to better understand the nucleotide sequence specificity that dictate where the binding and scission take place so that we could design specific reagents that target and cut DNA as we want, and then we can reassemble those cut segments into desired architectural motifs.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 20, 2019
- Source ID
- N000141912602
Entities
People
- Yayin Fang
Organizations
- Howard University
- Office of Naval Research
- United States Navy