97
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.
