Principles governing oligomer formation in amyloidogenic peptides.
Identifying the principles that describe the formation of protein oligomers and fibrils with distinct morphologies is a daunting problem. Here we summarize general principles of oligomer formation gleaned from molecular dynamics simulations of Abeta-peptides. The spectra of high free energy structures sampled by the monomer provide insights into the plausible fibril structures, providing a rationale for the 'strain phenomenon.' Heterogeneous growth dynamics of small oligomers of Abeta(16-22), whose lowest free energy structures are like nematic droplets, can be broadly described using a two-stage dock-lock mechanism. In the growth process, water is found to play various roles depending on the oligomer size, and peptide length, and sequence. Water may be an explicit element of fibril structure linked to various fibril morphologies.
Straub
John E
JE
Department of Chemistry, Boston University, Boston, MA 02245, USA. straub@bu.edu
Thirumalai
Devarajan
D
D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D003198:Computer Simulation; D019281:Dimerization; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D013816:Thermodynamics; D014867:Water / Q000737:chemistry / Q000378:metabolism
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D014867:Water