Project dates: 1 Apr 2010 - 31 Dec 2014

The metrological foundations underlying biomolecular structure and function are sparse and fail to keep pace with the demands of molecular medicine and the attempts to provide solutions to global health challenges such as viral epidemics, anti-microbial resistance and metastatic cancers.

Validated measurements and standardisation techniques are needed to enable any sustainable progress in this area and to advance our understanding of structure-activity links at the molecular and supramolecular levels, thereby providing key principles for rational drug design and molecular diagnostics.

This project aims to establish a comprehensive metrology infrastructure that will extend our understanding of key relationships between biomolecular structure, dynamics and function. This will be achieved by providing definitive structural measurements of polypeptides and their properties in native molecular and cellular environments. A sufficiently extensive international effort within the project will transform into a leading metrology centre generating major downstream economic and healthcare impacts. The scientific and technological methodologies developed will be used to validate generic rules, first design principles, to enable polypeptide sequence-to-function prediction.

This project addresses the most pressing measurement challenges pertaining to:

• incompleteness in detail of biomolecular structure-function relationships; and
• lack of biomolecular measurands, established reference methodologies and reference materials, and particularly those related to protein folding in native environments.

New solutions to these challenges will provide a measurement-based rationale for efficient sequence-to-function prediction approaches.

NPL staff involved with the project

Max Ryadnov, with the Biotechnology and Surface & Nanoanalysis groups

Collaborations

• Jason Crain, University of Edinburgh
• Glenn Martyna, IBM
• Isogenica Ltd
• Mologic Ltd
• Senexis Ltd
• PTB
• Joint Research Centre (JRC)
• NIST

Publications

• Prescriptive peptide design
  M. G. Ryadnov
  Amino Acids, Pept. Proteins., (Farkas and Ryadnov, eds.), RSC Publishing, 37, pages 190-237 (2012)
• Model systems for folding and tertiary contacts in peptides: a perspective from the physical sciences
  J. Crain
  Amino Acids, Pept. Proteins., (Farkas and Ryadnov, eds.), RSC Publishing, 37, pages 119-150 (2012).
• Farkas E, Ryadnov MG
  Amino Acids, Pept. Proteins., RSC Publishing 37, 270 pages (2012)
• Natively unfolded state for engineering nanoscale fibrillar arrays
  M. G. Ryadnov, D. I. Cherny
  Macromol. Biosci., 12 (2), pages 195-201 (2012)
• Membrane mediated regulation in free peptides of HIV-1 gp41: minimal modulation of the hemifusion phase
  E. Cerasoli, J. Ravi, C. R. Gregor, R. Hussain, G. Siligardi, G. J. Martyna, J. Crain, M. G. Ryadnov
  Phys. Chem. Chem. Phys., 14, pages 1277-1285 (2012)
• Arbitrary self-assembly of peptide extracellular microscopic matrices
  A. Bella, S. Ray, M. Shaw, M. G. Ryadnov
  Angew. Chem. Int. Ed., 51, pages 428-431 (2012)
• GeT peptides: a single-domain approach to gene delivery
  B. Lamarre, J. Ravi, M. G. Ryadnov
  Chem. Commun., 47, pages 9045-9047 (2011)
• Antibody recognition of a human chorionic gonadotropin epitope (hCGb_66-80) depends on local structure retained in the free peptide
  C. R. Gregor, E. Cerasoli, J. Schouten, J. Ravi, J. Slootstra, A. Horgan, G. J. Martyna, M. G. Ryadnov, P. Davis, J. Crain
  J. Biol. Chem., 286, pages 25016-25026 (2011)
• Recent contributions from solid-state NMR to the understanding of membrane protein structure and function
  P. J. Judge, A. Watts
  Curr. Opin. Chem. Biol., 15, pages 690-695 (2011)
• Autonomous folding in the membrane proximal HIV peptide gp41659-671: pH tuneability at micelle interfaces
  C. R. Gregor, E. Cerasoli, P. R. Tulip, M. G. Ryadnov, G. J. Martyna, J. Crain
  Phys. Chem. Chem. Phys., 13, pages 127-135 (2011)
• Self-assembling viral mimetics. One long journey with short steps
  B. Lamarre, M. G. Ryadnov
  Macomol. Biosci., 11, pages 503-513 (2011)
• Translational biophysics: physical sciences for molecular medicine
  M. G. Ryadnov, E. Cerasoli, G. J. Martyna, J. Crain
  Future Med. Chem., 2, pages 1633-1639 (2010)
• Conformational Plasticity in an HIV-1 Antibody Epitope
  R. Tulip, C. R. Gregor, R. Z. Troitzsch, G. J. Martyna, E. Cerasoli, G. Tranter, J. Crain
  J. Phys. Chem. B., 114, pages 7942-7950 (2010)