1. Theoretical investigating DNA binding properties in Rad51D as a way to find missing facts in Homologous Recombination Repair mechanism
Lecturer: Mohammad Taghizadeh
Bioinformatics PhD Student : Tehran University- IBB
Supervisors: Dr. Bahram Goliaei, Dr. Armin Madadker Sobhani
Faculty Members of Tehran University-IBB

2. Why using Bioinformatics algorithms and tools are important ?

3. HRR:

4. HRR: Structural Mechanism

5. Introduction: Rad51D as one of Rad51 Paralogs; What’s their duty
Mediator between Rad51 and RPA
DNA damage signaling

6. Introduction: What is missing
Structural Mechanism for Rad51 Paralogs roles in HRR

7. Methods: Modeller AutoDock Discovery Studio CueMol HyperChem
Molecular Dynamic simulation (Gromacs)
(PreDS Server)

8. Results:
SSDNA DSDNA ATP(walker motifs) interaction and probable roles of them

9. Results: ATP binding
Blind
Position specific

10. Results: ATP binding; Blind
Ligand: 1- ATP+Mg ATP more affinity with Mg ion
Poses: 1-Between two Walkers other sites (around DNA binding sites)
About other ATP-Rad51D poses we know that there is no ATPase activity in other positions

11. Results: ATP binding; Blind
Binding Energy: -5.9 kj/mol
Walker A Blue
Walker B Red
ATP + Mg ion Green

12. Walker A and B motifs in Rad51 and its Paralogs

13. Results: Rad51D-ATP binding; Position specific
Binding Energy: -7.2 kj/mol
Walker A Red
Walker B Blue
ATP + Mg ion Green
Critical LYS Yellow

14. Result-Discussion: Disparate requirements for the Walker A and B ATPase …
Walker B for Other paralogs interactions

15. Results: Rad51D-SSDNA binding

16. Results: Rad51D-DSDNA binding with Hex V6

17. Discussion:

18. Discussion: Paralogs domain mapping
For vertebrates these 5 paralogs but for lower animals rad52 and Rad57

19. Discussion: Questions without answers
Role of DSDNA interaction
Role of each one of 5 Paralogs
Rad51 Interactions with Paralogs
Mechanistic role in DNA damage signaling
Finding homologous DNA

20. References
Kawabata, M., T. Kawabata, and M. Nishibori, Role of recA/RAD51 family proteins in mammals. Acta Med Okayama, (1): p Amunugama, R., et al., RAD51 protein ATP cap regulates nucleoprotein filament stability. J Biol Chem, (12): p Miller, K.A., et al., Domain mapping of the Rad51 paralog protein complexes. Nucleic Acids Res, (1): p Wiese, C., et al., Disparate requirements for the Walker A and B ATPase motifs of human RAD51D in homologous recombination. Nucleic Acids Res, (9): p Chang, M.W., et al., Virtual screening for HIV protease inhibitors: a comparison of AutoDock 4 and Vina. PLoS One, (8): p. e Trott, O. and A.J. Olson, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem, (2): p Venkatraman, V. and D.W. Ritchie, Flexible protein docking refinement using pose-dependent normal mode analysis. Proteins, (9): p Ritchie, D.W. and V. Venkatraman, Ultra-fast FFT protein docking on graphics processors. Bioinformatics, (19): p Ritchie, D.W., Evaluation of protein docking predictions using Hex 3.1 in CAPRI rounds 1 and 2. Proteins, (1): p

22. PYROCOCCUS FURIOSUS