Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session I

44-POS Board 44 Molecular Simulation Studies on Large Scale Aggregation of Self-Assembling Amphiphilic Peptides Reveal Factors Governing Biomineralization Alok Jain 1,2 , Mara Jochum 2 , Christine Peter 1,2 . 1 University of Konstanz, P.O. Box 718, 78547, Konstanz, Germany, 2 Max Planck Institute for Polymer Research, Ackermannweg 10, 55128, Mainz, Germany. Biomineralization is the intricate process employed by living organisms to form minerals on preformed biological aggregates to build skeletal structures and shells. Rapaport and coworkers [1-3] have designed an important class of acidic residue-rich, self-assembling amphiphilic peptides that form hydrogels in bulk and, upon addition of ions to solution, enhance bone tissue regeneration. Human orthopedic conditions, such as osteoporosis, are a direct consequence of poorly orchestrated biomineralization. Deciphering the molecular mechanism of this vital yet poorly understood process is thus essential for the development of therapeutic approaches. Our study fills this void by revealing the factors that might promote formation of stable aggregates, akin to the extracellular matrix (ECM), and subsequent biomineralization events. We have used molecular dynamics simulations to obtain insight into the factors that govern the peptide aggregation and into the early stages of the biomineralization process. The effect of the various aspects of the peptide sequence on aggregate stability and ion-peptide interactions were studied. Our results reveal that peptides with proline as terminal residues formed more strongly ordered aggregates compared to those with phenylalanine. Aggregate stability was also found to be influenced by the nature of the side-chain groups of the peptides. Simulations in the presence of various ions showed how the ions influence aggregate stability in a side-chain-dependent manner. Our simulations also captured the crystallization events which might occur during the early stages of biomineralization. [1] Rapaport, H.; Kjaer, K.; Jensen, T. R.; Leiserowitz, L.; Tirrell, D. A. J. Am. Chem. Soc. 2000, 122, 12523. [2] Rapaport, H.; Grisaru, H.; Silberstein, T. Adv. Funct. Mater. 2008, 18, 2889. [3] Amosi, N.; Zarzhitsky, S.; Gilsohn, E.; Salnikov, O.; Monsonego-Ornan, E.; Shahar, R.; Rapaport, H. Acta Biomater. 2012, 8, 2466.

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