Residual structure in disordered peptides and unfolded proteins from multivariate analysis and ab initio simulation of Raman optical activity data

Zhu, F., Kapitan, J., Tranter, G.E., Pudney, P.D.A., Isaacs, N.W., Hecht, L. and Barron, L.D. (2008) Residual structure in disordered peptides and unfolded proteins from multivariate analysis and ab initio simulation of Raman optical activity data. Proteins: Structure Function and Bioinformatics, 70(3), pp. 823-833. (doi: 10.1002/prot.21593)

Abstract

Vibrational Raman optical activity (ROA), measured as a small difference in the intensity of Raman scattering from chiral molecules in right- and left-circularly polarized incident light, or as the intensity of a small circularly polarized component in the scattered light, is a powerful probe of the aqueous solution structure of proteins. The large number of structure-sensitive bands in protein ROA spectra makes multivariate analysis techniques such as nonlinear mapping (NLM) especially favorable for determining structural relationships between different proteins. We have previously used NLM to map a large dataset of peptide, protein, and virus ROA spectra into a readily visualizable two-dimensional space in which points close to or distant from each other, respectively, represent similar or dissimilar structures. As well as folded proteins, our dataset contains ROA spectra from many natively unfolded proteins, proteins containing both folded and unfolded domains, denatured partially structured molten globule and reduced protein states, together with folded proteins containing little or no alpha-helix or beta-sheet. In this article, the relative positions of these systems in the NLM plot are used to obtain information about any residual structure that they may contain. The striking differences between the structural propensities of proteins that are unfolded in their native states and those that are unfolded due to denaturation may be responsible for their often very different behavior, especially with regard to aggregation. An ab initio simulation of the Raman and ROA spectra Of an alanine oligopeptide in the poly(L-proline) II-helical conformation confirms previous suggestions that this conformation is a significant structural element in disordered peptides and natively unfolded proteins. The use of ROA to identify and characterize proteins containing significant amounts of unfolded structure will, inter alia, be valuable in structural genomics/proteomics since unfolded sequences often inhibit crystallization.

• Item Type: Articles
• Keywords: AB-INITIO ALANINE AQUEOUS-SOLUTION BEHAVIOR Chiral CHIRAL MOLECULES CONFORMATION CRYSTALLIZATION DIFFERENCE disordered structure DOMAIN INFORMATION INTRINSICALLY UNSTRUCTURED PROTEINS LIGHT MOLECULE MOLECULES multivariate analysis MULTIVARIATE-ANALYSIS NMR OLIGOPEPTIDES OPTICAL-ACTIVITY peptide PEPTIDES poly(L-proline) II helix POLY(L-PROLINE)-II HELIX POLYPROLINE-II HELIX PROTEIN PROTEINS RAMAN Raman optical activity RAMAN-SCATTERING SCATTERING SEQUENCE SEQUENCES SIMULATION SPECTRA SPECTRUM STATE STATES structural genomics/proteomics Structure SYSTEM SYSTEMS UNFOLDED PROTEINS VIBRATIONAL CIRCULAR-DICHROISM
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kapitan, Dr Josef and Hecht, Dr Lutz and Barron, Professor Laurence and Zhu, Dr Fujiang and Isaacs, Professor Neil
• Authors: Zhu, F., Kapitan, J., Tranter, G.E., Pudney, P.D.A., Isaacs, N.W., Hecht, L., and Barron, L.D.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Proteins: Structure Function and Bioinformatics
• ISSN: 0887-3585

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
46699	1	Solution structures of natural and synthetic chiral oligomers and polymers from ab initio simulations of Raman Optical Activity data.	Lutz Hecht	Engineering & Physical Sciences Research Council (EPSRC)	EP/F029713/1	Chemistry