Estimation of peptide helicity from circular dichroism using the ensemble model

Zavrtanik, Uroš (author), Lah, Jurij (author), Hadži, San (author)

An established method for the quantitation of the helix content in peptides using circular dichroism (CD) relies on the linear spectroscopic model. This model assumes an average value of the helix-length correction for all peptide conformers, irrespective of the length of the helical segment. Here we assess the validity of this approximation and introduce a more physically realistic ensemble-based analysis of the CD signal in which the length correction is assigned specifically to each ensemble conformer. We demonstrate that the linear model underestimates peptide helicity, with the difference depending on the ensemble composition. We developed a computer program that implements the ensemble model to estimate the peptide helicity. Using this model and the CD data set covering a broad range of helicities, we recalibrate CD baseline parameters and redetermine helix–coil parameters for the alanine-rich peptide. We show that the ensemble model leverages small differences in signal between conformers to extract more information from the experimental data, enabling the determination of several poorly defined quantities, such as the nucleation constant and heat capacity change associated with helix folding. Overall, the presented ensemble-based treatment of the CD signal, together with the recalibrated values of the spectroscopic baseline parameters, provides a coherent framework for the analysis of the peptide helix content.

• Language: English
• Keywords: circular dichroism, helix-coil transition, Lifson-Roig model, helix ellipticity, polylanine alpha-helix folding thermodynamics, Markov modeling, molecular structure, optical properties, peptides, proteins, spectroscopy
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: Str. 2652-2663
• Numbering: Vol. 128, iss. 11
• PID: 20.500.12556/RUL-155243
• UDC: 577.322
• ISSN on article: 1520-6106
• DOI: 10.1021/acs.jpcb.3c07511
• COBISS.SI-ID: 189763843
• Publication date in RUL: 21.03.2024

Record is a part of a journal

• Title: The journal of physical chemistry. B
• Shortened title: J. phys. chem., B Condens. mater. surf. interfaces biophys.
• Publisher: American Chemical Society
• ISSN: 1520-6106
• COBISS.SI-ID: 14241063

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: cirkularni dikroizem, prehod vijačnica-naključni klobčič, Lifson-Roigov model, eliptičnost alfa-vijačnice, termodinamika zvitja