Assembly dynamics of two-β sheets revealed by molecular dynamics simulations
Abstract
The assembly dynamics of two β sheets with different initial separation distances are explored by multiple all-atom molecular dynamics simulations with the presence of explicit water solvent. The β sheet is composed of seven identical peptides in an antiparallel fashion. The peptide sequence is the 20-29 segment of human Islet amyloid polypeptide. Our simulations show that the assembly occurs not only in the lateral direction but also along the longitudinal direction, which provides a new insight into the assembly pathway at the early stage of fibril elongation. Based on Poisson-Boltzmann free energy analysis and quasiharmonic configuration entropy estimation, the entropic contribution is found to play an important role in the longitudinal assembly. Moreover, a possible oligomeric state with cyclic form is suggested based on one assembly model found in the simulations, illustrating the polymorphic nature of aggregation of the amyloidogenic peptide.
- Publication:
-
Journal of Chemical Physics
- Pub Date:
- April 2009
- DOI:
- 10.1063/1.3123532
- Bibcode:
- 2009JChPh.130p4709X
- Keywords:
-
- 87.15.ap;
- 87.15.B-;
- 87.15.H-;
- 87.15.Qt;
- Molecular dynamics simulation;
- Structure of biomolecules;
- Dynamics of biomolecules;
- Sequence analysis