284176 A Computational Study of the Self-Assembly of Diblock Peptides

Wednesday, October 31, 2012: 4:40 PM
414 (Convention Center )
Daniel Forciniti, Cbe, Missouri University of Science and Technology, Rolla, MO and Fazeem Rehman, Chem. Eng., Missouri S&T, Rolla, MO

Model compounds have been used to study the formation of amyloid deposits in a controlled manner and to address the question:  Are all proteins capable of forming amyloid deposits?  .

We have identified a family of diblock peptides that forms amyloid fibrils at moderate conditions (pH 4 and 60 oC).  The kinetics of fibril formation seems to be affected by the overall length of the peptide but not by their composition (beyond some critical block concentrations).  Longer peptides form fibrils faster than shorter ones.  Fibrillation depends on minute differences in amino acid composition.  For example, diblock peptides of lysine and isoleucine form fibrils after a critical length is reached whereas diblock peptides of lysine and leucine do not form fibrils irrespective of the length of the blocks.  The fibrillation process escapes a simple explanation.

To advance our knowledge about the formation of fibrils by this type of peptides we have started a computationally study.  A Monte Carlo code developed by our group years ago (Mungikar and Forciniti, Biomacromolecules, 7:239 (2006)) was modified to to handle the simulation of multiple peptide molecules (the old code was written for an infinite dilution situation).   Most simplified peptide models will not be able to capture the differences between isoleucine and leucine that seems to be critical in our case.  Unfortunately and all-atom simulation in the presence of explicit water will allow us only to scratch the surface of the nucleation process (fewer than 10 peptides) but it will be prohibitive to study the peptide concentrations found during fibril formation.  To overcome this problem,  we used an all atoms model for the peptides but an implicit model to account for solvent effects.  The  solvent is treated implicitly using  a peptide density dependent switch function that accounts for intra and intermolecular hydrogen bonding and hydrophobic interactions.  Initial simulations suggest the initial formation of amorphous aggregates (fibril nuclei) formed by multiple contacts of the non polar amino acids.  Slow conformational changes are then induced by repulsions between the charged lysine groups.

Extended Abstract: File Not Uploaded
See more of this Session: Self-­Assembly in Solution II
See more of this Group/Topical: Engineering Sciences and Fundamentals