Protein folding and misfolding: a paradigm of self-assembly and regulation in complex biological systems

M Vendruscolo, J Zurdo, C E MacPhee, C M Dobson, Cait MacPhee

Research output: Contribution to journalArticlepeer-review

Abstract

Understanding biological complexity is one of the grand scientific challenges for the future. A living organism is a highly evolved system made up of a large number n of interwoven molecular networks. These networks primarily involve proteins, the macromolecules that enable and control virtually every chemical process that takes place in the cell. Proteins are also key elements in the essential characteristic of living systems, their ability to function and replicate themselves through controlled molecular interactions. Recent progress in understanding the most fundamental aspect of polypeptide self-organization, the process by which proteins fold to attain their active conformations, provides a global platform to gain knowledge about the function of biological systems and the regulatory mechanisms that underpin their ability to adapt to changing conditions. In order to exploit such progress effectively, we are developing a variety of approaches, including procedures that use experimental data to restrain the properties of complex systems in computer simulations, to describe their behaviour under a wide variety of conditions. We believe that such approaches can lead to significant advances in understanding biological complexity, in general, and protein folding and misfolding in particular. These advances would contribute to: a more effective exploitation of the information from genome sequences; more rational therapeutic approaches to diseases, particularly those associated with ageing; the responsible control of our own evolution; and the development of new technologies based on mimicking the principles of biological self-assembly, for instance in nanotechnology. More fundamentally, we believe that this research will result in a more coherent understanding of the origin, evolution and functional properties of living systems.

Original languageEnglish
Pages (from-to)1205-1222
Number of pages18
JournalPhilosophical Transactions A: Mathematical, Physical and Engineering Sciences
Volume361
Issue number1807
DOIs
Publication statusPublished - 13 Jun 2003

Keywords

  • protein folding
  • misfolding diseases
  • biological complexity
  • self-organization
  • nanotechnology
  • biological evolution
  • BETA-SHEET PROTEINS
  • AMYLOID FIBRIL
  • HUMAN-DISEASE
  • HUMAN GENOME
  • AGGREGATION
  • MECHANISM
  • PATHWAYS
  • DESIGN
  • NANOSTRUCTURES
  • SIMULATIONS

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