Structure and sequence determinants of aggregation investigated with molecular dynamics

Front Biosci (Landmark Ed). 2009 Jan 1;14(2):523-39. doi: 10.2741/3260.

Abstract

Spontaneous self-assembly and amyloid formation are a general property of many polypeptides and the information controlling these processes is encoded in the sequence. This determines the form and structural features of the interacting partners that regulate the properties of the final aggregates. Understanding the correlations between sequence, structure and dynamics in peptides and proteins at an atomistic level of resolution still represents one of the grand challenges of modern biological chemistry. In this context, computer simulations represent a valuable approach to understand recognition and spontaneous self-organization, processes that cannot be directly observed experimentally. Herein, we will discuss cases illustrating the extent to which simulations can be used to understand the self-organization properties of natural and designed amyloidogenic peptide sequences. The simulations provide evidence for the influence of specific interactions with well defined stereochemical constraints on fibril formation. The results from our and other groups suggest that simulations can be applied to detect the critical physico-chemical determinants of a certain process and can be helpful in the design of new chemical systems and experiments.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amyloid / chemistry*
  • Models, Molecular
  • Peptides / chemistry*
  • Protein Conformation

Substances

  • Amyloid
  • Peptides