SEB’e Bağlanan Tekrarlı Peptid Dizilimlerinin REMD Çalışması

Year 2017, Volume: 7 Issue: 1, 206 - 217, 01.01.2017

Nesrin Kılıç Kadir Demir

Abstract

Değişikliğe uğramış peptitlerin konformasyonel farklılıklarının, afinite üzerinde rol oynayıp oynamadığını araştırdık. Bu amaçla, staphylococcal enterotoxin B SEB ’e bağlanma afinitesini değiştiren tekrarlı peptit dizilimlerinin ikincil yapı eğilimlerini ve konformasyonel durumlarını elde etmek için Replica Exchange Moleküler Dinamik REMD simülasyonlar yaptık. REMD simülasyonlardan elde edilen sonuçlar bu tekrarlı peptit dizilimlerinin ikincil yapılarının tüm sıcaklıklar için az miktarda heliks ve β-bridge yapılarla birlikte çoğunlukla random coil, bend ve turn yapılar olduğunu gösterdi. Bunların yanısıra, dizilimlerin tekrarlanmasıyla random coil yapıların yüzdesi azalırken, bend yapılarda artış gözlenmiştir. Bu sonuçlar Circular Dicroism CD spektroskopiden elde edilen sonuçlarla uyumludur. Temel Bileşen Analizi PCA vasıtasıyla, peptit dizilimlerinin serbest enerji yüzeyleri elde edilmiş ve birkaç yerel minimum bulunmuştur. Bu minimumlara karşılık gelen ikincil yapılar her iki peptit için de çoğunlukla coil, bend ve turn yapılara sahiptir. Bu baskın yapılara ek olarak bir de önemli miktarda heliks ve β-bridge yapılar göze çarpmıştır. Peptit dizilimlerini tekrar sayısı arttıkça random coil yapıların yüzdesi azalır ve random coil yapılardaki bu dönüşüm seçilen sıcaklık ve bölgeye bağlı olarak bend, turn, heliks ve β-bridge yapılardaki artış şeklinde ortaya çıkar. Sonuçlar, tekrarlı peptit dizilimlerinin ikincil yapı eğilimleri ve afinite arasında doğrudan bir ilişki görüntülenemediğini işaret etmiştir

Keywords

Serbest enerji yüzeyi, Peptit ligand, Temel bileşen analizi, Kopya değiş-tokuş moleküler dinamik, SEB’e bağlanan peptitler, İkincil yapı

The Study of REMD Simulation of SEB-Binding Repetitive Peptide Sequences

Abstract

We investigated whether the conformational differences of modified peptides play a role for affinity or not. For this purpose, we have performed the replica exchange molecular dynamic simulation REMD to obtain the conformational states and secondary structural propensities of repetitive peptide sequences changed the affinity of binding to staphylococcal enterotoxin B SEB . The results obtained from REMD simulations have shown that the secondary structures of these repetitive peptide sequences were mainly random coil, bend and turn structures with a small amount of helix and β-bridge structures for all temperatures. Besides it was shown that, with repeating the sequence, while the percentage of random coil structures decreased, the ones of bend structures increased. These results are consistent with the ones which obtained from circular dicroism spectroscopy. In terms of principal component analysis PCA , the free energy landscapes of peptide sequences were obtained and found several local minima. The secondary structures corresponding with these minima have mainly coil, turn and bend structures for both peptides. In addition to these dominant structures considerable amount of helix and β-bridge structures were also outstanding. Its observed that while the number of repetition of peptide sequence increases, the percentage of random coil structures are decreases and this transformation in the random coil structures emerges in the form of increases in the rates of bend, turn, helix and β-bridge structures with the chosen temperature and region. The results pointed that it was not monitored a directly relationship between the affinity and secondary structures propensities of repetitive peptides.

Keywords

replica exchange molecular dynamics, secondary structure, peptide ligands, principal component analysis, free energy landscape, SEB-binding peptides

References

• Berendsen, HJC., Postma, JPM., van Gusteren, WF., Hermans, J. 1981. Interaction models for water in relation to protein hydration. D. Rediel: Dordrect, 331-342.
• Demir, K., Kılıç N., Dudak, FC., Boyacı, İH., Yaşar, F. 2014. The investigation of the secondary structure propensities and free-energy landscapes of peptide ligands by replica exchange molecular dynamics simulations. Mol. Simul., 40: 1015-1025.
• Dill, KA. 1990. Dominant forces in protein folding. Biochemistry, 29(31):7133-7155.
• Dudak, FC., Soykut, EA., Oğuz, ME., Yaşar, F., Boyacı, İH. 2010. Thermodynamic and structural analysis of interactions between peptide ligands and SEB. J. Mol. Recognit., 23: 369– 378.
• Dudak, FC., Kılıç, N., Demir, K., Yaşar, F., Boyacı, İH. 2012. Enhancing the Affinity of SEB-Binding Peptides By Repeating their Sequence. Biopolymers (Pept. Sci.), 98: 145- 154.
• Geyer, CJ. 1992. Practical Markov chain Monte Carlo. Stat. Sci., 7: 473-483.
• Hahn, IF., Pickenhahn, P., Lenz, W., Brandis, HJ. 1986. An avidin-biotin ELISA for the detection of staphylococcal enterotoxins A and B. Immunol Methods, 92: 25–29.
• Hansmann, UHE. 1997. Paralel tempering algorithm for conformational studies of biological molecules. Chem. Phys. Lett., 314: 140-150.
• Hansmann, UHE. 2010. Temperature random walk sampling of protein configurations. Physica A, 389: 1400-1404.
• Harteveld, JLN., Nieuwenhuizen, MS, Wils, ERJ. 1997. Detection of Staphyloccoccal enterotoxin B employing a piezoelectric crystal immunosensor. J. Microbiol Method, 7: 661–667.
• Homola, J., Dostalek, J., Chen, S., Rasooly, A., Jiang, S., Yee, SS. 2002. Spectral surface plasmon resonance biosensor for detection of staphylococcal enterotoxin B in milk. Int. J. Food. Microbiol., 7: 61–69.
• Hukushima, K., Nemoto, K. 1996. Exchange Monte Carlo method and application to spin glass simulation. J. Phys. Soc., 65: 1604-1608.
• Humphrey, W., Dalke, A., Schulten, K. 1996. VMD: Visual molecular dynamics. J. Mol. Graph., 14: 33-38.
• Jorgensen, WL., Severance, DL. 1990. Aromatic-aromatic interactions: free energy profiles for the benzene dimer in water, chloroform, and liquid benzene. J. Am. Chem. Soc., 112: 4768-4774.
• Kabsch, W., Sander, C. 1983. Dictionary of protein secondary structure: pattern recognition of hydrogen bonded and geometrical features. Biopolymers, 22: 2577–2637.
• King, KD., Anderson, GP., Bullock, KE., Regina, MJ., Saaski, EW., Ligler, FS. 1999. Detecting staphylococcal enterotoxin B using an automated fiber biosensor. Biosens. Bioelectron, 14: 163–170.
• Kouza, M., Hansmann, UHE. 2011. Velocity scaling for optimizing replica exchange molecular dynamics. J. Chem. Phys., 134: (044124) 1-6.
• Limongelli, V., Marinelli, L., Coscanati, S., La Motta, C., Sartini, S., Mugnaini, L., Da Settimo, F., Novellino, E., Parrinello, M. 2012. Sampling Protein Motion and Solvent Effect During Ligand Binding. Proc. Natl. Acad. Sci., 109: 1467-1472.
• Lin, HC., Tsai, WC. 2003. Piezoelectric crystal immunosensor for the detection of staphylococcal enterotoxin B. Biosens. Bioelectron, 18: 1479–1483.
• Maisuradze, GG., Leitner, DM. 2007. Free Energy Landscape of a Biomolecule in Dihedral Principal Component Space: Sampling Convergence and Correspondence Between Structures and Minima. PROTEİNS, 67: 569-578.
• Maisuradze, GG., Liwo, A., Schrega, HA. 2009. How Adequate are one and two dimensional free energy landscapes for protein folding dynamics. Phys. Rev. Lett., 102: (238102) 1-4.
• Marrack, P., Kappler, J. 1990. The staphylococcal enterotoxins and their relatives. Science, 248: 705–711.
• Mobley, DL., Bayly, CL.. Cooper, MD., Shirts, MR., Dill, KA. 2009. Small Molecule Hydration Free Energies in Explicit Solvent: An Extensive Test of Fixed-Charge Atomistic Simulations. J. Chem. Theory Comput., 5: 350-358.
• Mobley, DL., Klimovich, PV. 2012. Perspective: Alchemical Free Energy Calculations for Drug Discovery. J. Chem. Phys., 137: 230901.
• Naimushin, AN., Soelberg, SD., Nguyen, DK., Dunlap, L., Bartholomew, D., Elkind, J., Melendez, J., Furlong, C.E. 2002. Detection of Staphyloccoccus aureus enterotoxin B at femtomolar levels with a miniature integrated two channel surface plasmon resonance (SPR) sensor. Biosens. Bioelectron, 17: 573–584.
• Nemety, G., Scheraga, HA. 1962. The Structure of Water and Hydrophobic Bonding in Proteins III. The Thermodynamic Properties of Hydrophobic Bonds in Proteins. J. Phys. Chem., 66(10): 1773-1789.
• Pace, CN., Shirley, BA., Mcnutt, M., Gajiwala, K. 1996. Forces contributing to the conformational stability of proteins. FASEB J., 10: 75-83.
• Park, CE., Akhtar, M., Rayman, MK. 1994. Evaluation of a commercial enzyme immunoassay kit (RIDASCREEN) for detection of staphylococcal enterotoxins A, B, C, D, and E in foods. Appl. Environ. Microb., 60: 677–681.
• Patriksson, A., van der Spoel, D.A. 2008. Temperature predictor for parallel tempering simulations. Phys. Chem., 10: 2073-2077.
• Ren, P., Ponder, J.W. 2002. Consistent treatment of interand intramolecular polarization in molecular mechanics calculations. J. Comp. Chem., 23: 1497-1506.
• Slavik, R., Homola, J., Brynda, E. 2002. A miniature fiber optic surface plasmon resonance sensor for fast detection of Staphyloccoccal enterotoxin B. Biosens. Bioelectron., 17: 591– 595.
• Sugita, Y., Okamoto, Y. 1999. Replica-exchange molecular dynamics method for protein folding. Chem. Phys. Lett., 314: 141-151.
• Swendsen, R., Wang, J. 1986. Replica Monte Carlo of spinglasses. Phys. Rev. Lett., 57: 2607-2609.
• Swift, RV., Amaro, RE. 2013. Back to the Future: Can Physical Models of Passive Membrane Permeability Help Reduce Drug Candidate Attrition and Move Us Beyond QSPR? Chem. Biol. Grug Des., 81: 61-71.
• Van der Spoel, D., Lindahl, E., Hess, B., Groenhof, G., Mark, A.E., Brendsen HJ. 2005. Gromacs: Fast, Flexible, and free. J. Comp. Chem., 26: 1701-1718.
• Warshel, A. 1981. Calculations of Enzymic Reactions: Calculations of pKa, Proton Transfer Reactions and General Acid Catalysis Reactions in Enzymes. Biochemistry, 20: 3167- 3177.