Dynamical Resolution of QM/MM Near-UV Circular Dichroism Spectra of Low-Symmetry Systems

Near-UV circular dichroism (CD) spectroscopy is a widely used method that provides, among others, information about the tertiary structure of biomolecular systems such as proteins, RNA, or DNA. Experimental near-UV CD spectra of proteins reflect the CD signals averaged over the many conformations th...

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Bibliographic Details
Main Authors: Jérémy Morere, Tanguy Leyder, Catherine Michaux, Claude Millot, Emmanuelle Bignon, Thibaud Etienne
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Chemistry
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Online Access:https://www.mdpi.com/2624-8549/7/2/63
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Summary:Near-UV circular dichroism (CD) spectroscopy is a widely used method that provides, among others, information about the tertiary structure of biomolecular systems such as proteins, RNA, or DNA. Experimental near-UV CD spectra of proteins reflect the CD signals averaged over the many conformations that these systems can adopt. Theoretical approaches have been developed to predict such spectroscopic properties and link modeled conformations of complex biosystems to easily accessible experimental data, without having the resort to costly structural biology techniques. However, these predictions are mostly generated on the basis of a single experimental structure, missing the dynamic information reflecting the protein conformational variability. Here, we describe a complete reformulation of the theoretical foundations behind the prediction of CD spectra. We propose a QM/MM-based automated pipeline that generates an average near-UV CD spectrum from a given MD ensemble in a fast manner based on these theoretical considerations and further test it on protein systems. This pipeline has been implemented in an open-source program called DichroProt.
ISSN:2624-8549