Optimized Structure of Monoubiqutinated FANCD2 (Human) at Lys 561: A Theoretical Approach

Abstract

The Fanconi anaemia pathway repairs DNA interstrand crosslinking damage (ICLs) in the genome. Mono ubiquitination in FANCD2 and FANCI is very crucial for DNA repairing. Our major focus is on the human FANCD2 protein and its crucial monoubiquitination process at Lys561. Our intention is to give insight on the importance of mono ubiquitination process, that is what structural change is exactly taking place after ubiquitination. Crystal structure of the monoubiquitinated FANCD2 (of any organism ) is not available in any data base, here I have reported the optimized structure of the human monoubiquitinated (Lys 561) FANCD2. No software or web server directly gives the monoubiquitinated product, so we have hypothesised a process to do the monoubiquitination, a post translational modification and validated that on applying on simplest monoubiquitinated protein, diubiquitin. We have predicted the structure of monoubiquitinated protein theoretically by doing protein- protein docking followed by molecular dynamic simulation. We have found that there is a large structural difference between FANCD2 and monoubiquitinated FANCD2. We have done docking studies and found that DNA is getting bound in dissimilar fashion with FANCD2 and monoubiquitinated FANCD2.

Keywords: Fanconi Anemia Pathway, FANCD2 protein, monoubiquitination, protein-protein docking, Molecular dynamic simulation