Optimized structure of monoubiquitinated FANCD2 (human) at Lys 561: a theoretical approach.

Fanconi anaemia pathway repairs inter-strand cross linking damage (ICL) of the DNA. Monoubiquitination of FANCD2 and FANCI is very crucial for ICL repairing. In this work we have tried to understand the monoubiquitinated FANCD2 structure, which facilitates the FANCD2 for binding the damage part of the chromatin. Crystal structure of the monoubiquitinated FANCD2 alone is not available, therefore we have modelled the optimized structure of the human monoubiquitinated (Lys 561) FANCD2. As there is no suitable software or web server we have developed a method for building up monoubiquitinated product and validated on simplest monoubiquitinated protein, diubiquitin. We have predicted the structure of human monoubiquitinated FANCD2 by using our method and studied the interaction with DNA by docking studies. Molecular Dynamics (MD) simulation has been used to understand the stability of the structure. Large structural differences have been observed between FANCD2 and monoubiquitinated FANCD2. Docking studies with DNA suggest that the binding site varies for the FANCD2 and monoubiquitinated FANCD2.Communicated by Ramaswamy H. Sarma.