Computer Simulations Aimed at Exploring Protein Aggregation and Dissociation

Abstract

Protein aggregation can lead to well-defined structures that are functional, but is also the cause of the death of neuron cells in many neurodegenerative diseases. The complexity of the molecular events involved in the aggregation kinetics of amyloid proteins and the transient and heterogeneous character of all oligomers prevent high-resolution structural experiments. As a result, computer simulations have been used to determine the atomic structures of amyloid proteins at different association stages as well to understand fibril dissociation. In this article, we first review the current computer simulation methods used for aggregation with some atomistic and coarse-grained results aimed at better characterizing the earlyformed oligomers and amyloid fibril formation. Then we present the applications of non-equilibrium molecular dynamics simulations to comprehend the dissociation of protein assemblies.

Disassembly of Amyloid Fibril with Infrared Free Electron Laser

“…Various fibrils from lysozyme (129 residues), insulin (51 residues), DFNKF (5 residues), polyglutamine (69 residues), Aβ (42 residues), GNNQQNY (7 residues), and β2-microglobulin peptide (11 residues) can be dissociated to their non-fibril states, although the disassembly patterns are slightly various depending on the amino acid sequences. In addition, those experimental results were arguably evidenced by molecular dynamic simulations [ 62 , 63 , 64 , 65 , 66 ]. Interestingly, the conversion from β-sheets to α-helices is observed in all types of amyloid proteins.…”