Assembly dynamics of two-beta sheets revealed by molecular dynamics simulations.
The assembly dynamics of two beta sheets with different initial separation distances are explored by multiple all-atom molecular dynamics simulations with the presence of explicit water solvent. The beta 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.
Xu
Weixin
W
School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.
Ping
Jiang
J
Li
Weifeng
W
Mu
Yuguang
Y
D000682:Amyloid / Q000737:chemistry*; D003198:Computer Simulation; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D058228:Islet Amyloid Polypeptide; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D014867:Water