Designing a new tetrapeptide to inhibit the BIR3 domain of the XIAP protein via molecular dynamics simulations

Mahnam, Karim; Mirahmadi Babaheidari, Fatemeh

doi:10.29252/nbr.5.2.168

Designing a new tetrapeptide to inhibit the BIR3 domain of the XIAP protein via molecular dynamics simulations

Authors

Karim Mahnam

Fatemeh Mirahmadi Babaheidari

Shahrkord University

https://doi.org/10.29252/nbr.5.2.168

Abstract

The XIAP protein is a member of apoptosis proteins family. The XIAP protein plays a central role in the inhibition of apoptosis and consists of three Baculoviral IAP Repeat domains. The BIR3 domain binds directly to the N-terminal of caspase-9 and therefore it inhibits apoptosis. N-terminal tetrapeptide region of SMAC protein can bind to BIR3, inhibit it and subsequently induce apoptosis. In this study, fifteen tetrapeptides were docked into the BIR3 domain and then 10 ns molecular dynamics simulations were performed on each of the BIR3-peptide complex obtained from docking. MM/PBSA method was subsequently used to calculate the binding free energy of peptides to BIR3. The results of MM/PBSA method were in good coordination with docking and existing expermental results. The results showed the most potent peptides with the lowest binding free energy for binding to BIR3 included ATPF, AKPW and ARPF peptides. Also, investigation of bonds between these peptides and BIR3 domain in the final structure of complexes showed that Leu 307, Thr 308, Glu 314 and Tyr 324 of the BIR3 domain were essential for binding of peptides. Energy decomposition results for binding these peptides to the BIR3 domain during MD simulation was inconsistent with previous results and approved the roles of the same residues. The higher affinity of these peptides relative to native peptide (AVPI) and comparing them with other peptides revealed that the existence of positive charge in the second position and the existence of the aromatic group in the fourth position led to more binding affinity.

Keywords

Apoptosis

cancer

docking

MM/PBSA method

20.1001.1.24236330.1397.5.2.11.1

Agrawal, R.L. 1991. Seed technology. Second edition. – Oxford and IBH press. New York and London. pp: 445.

Akhavan-armaki, M., Hashemi, M., Azarnivand, H., Osare, M. H., Jafari, A.A. and Tavili A. 2013. Effect of drought stress on growth and germination characteristics of three genotype of Agropyron trichophorum. – Desert Eco. Eng. J. 2: 9-14.

Armand, N., Amiri, H. and Ismaeili, A. 2015. Effect of methanol on germination characteristics of bean (Phaseolus vulgaris L. cv. Sadry) under drought stress condition. – Iran. J. Pulses Res. 6: 42-53.

Asadi, A. 2009. Investigation of salinity stress on seed germination of Trigonella foenum subsp. graecum – J. Biochem. Sci. 4: 1152-1155.

Dini, M. 2006. Scientific name of medicinal plants used in traditional medicine. – Forest and Rangeland Res. Inst. Pub. Iran. 299– 300.

Fabian, A., Jager, K. and Barnabas, B. 2008. Effects of drought and combined drought and heat stress on germination ability and seminal root growth of wheat (Triticum aestivum L.) seedlings. – J. Acta Biologica 52: 157-159.

Farhadi, H., Azizi, M. and Nemati, S.H. 2015. Effect of salinity on traits related with performance in eight native population of fenugreek (Trigonella foenum subsp. graecum). – Iran. J. Field Crops Res. 12: 862-870.

Gamze, O., Mehmet Demir, K.A.Y. and Mehmet, A.T.A. 2005. Effects of salt and drought stresses on germination and seedling growth of pea (Pisum sativum L.). – Turk. J. Agri. 29: 237- 242.

Hasanzadeh, A., Rezazade, S.H., Shamsa, S. F., Dolat Abadi, R. and Zaringhalam, J. 2010. A review on the medical and phytochemical properties of fenugreek. – J. Medicin. Plant. 2: 1-18.

Ji, X.M., Raveendran, M., Oane, R., Ismail, A. Lafitte1, R., Bruskiewich, R., Cheng, S.H. and Bennett, J. 2005. Tissue-specific expression and drought responsiveness of cell-wall invertase genes of rice at flowering. – Plant Mol. Biol. 59: 945-964.

Jongdee, B., Fukai, S. and Cooper, M. 2002. Leaf water potential and osmotic adjustment as physiological traits to improve drought tolerance in rice. – Field Crops Res. 79: 153-163.

Liu, M., Li, M., Liu, K. and Sui, N. 2015. Effects of drought stress on seed germination and seedling growth of different maize varieties. – J. Agri. Sci. 7: 231-240.

Michel, B.E. and Kaufman, M.R. 1973. The osmotic potential of polyethylene glycol 6000. – Physiol. 51: 914-916.

Khalid, M. N., Iqbal, H.F., Tahir, A. and Ahmad, A.N. 2001. Germination potential of chickpeas (Cicer arietinum L.) under saline condition. – J. Biol. Sci. 4: 395-396.

Mantovani, A and Iglesias, R.R. 2010. The effect of water stress on seed germination of three terrestrial bromeliads from restinga. – Braz. J. Bot. 33: 201-205.

Mensah, J. K., Obadoni, B.O., Eruotor, P.G. and Onome, F. 2006. Simulated flooding and drought effects on germination, growth and yield parameters of sesame (Sesamum indicum L.). – Afric. J. Biol. 5: 1249-1253.

Roumani, A. and Ehteshami, M. 2014. Effect of different levels of salinity stress on seed germination and early growth of fenugreek (Trigonella foenum L.) seedling. – Iran. J. Seed Res. 1: 33-45.

Parmer, M.T. and More, R.P. 2008. Carbowax 6000, Maintol, Sodiumchloride for simulating drought condition in germination studies of corn (Zea mays) of strong and weak vigor. – Agro. J. 60: 192-195.

Zaheer Ahmed, M. and Ajmal Khan, M. 2010. Tolerance and recovery responses of playa halophytes to light, salinity and temperature stresses during seed germination. – Flora Morph. Distribut. Func. Eco. Plants. 205: 764-771.

Zebarjadi, A.R., Soheilikhah, Z.H., Ghasempour H.R. and Vaisipour, A. 2012. Effect of drought-induced stress by PEG6000 on physiological and morphological traits of Safflower (Carthamus tinctorius) seed germination in order to selection of drought tolerant genotypes. – Iran. J. Boil. 25: 252-263.