Mechanisms of protein circular dichroism: insights from computational modeling

Chirality is a fundamental property of molecular systems, and stereoselectivity underlines many fundamental biomolecular processes like biological recognition and catalysis. Circular dichroism (CD) which is a consequence of molecular chirality is an important method for the investigation of protein structure and structural changes during interactions with ligands, mutations, and folding. The development of computational methods allows powerful insight to be provided into the mechanisms of generation of CD spectra in complex systems as proteins and to explain experimental data, to validate predicted structures, and to explain fine details of biomolecular interactions. In this chapter, we provide a survey on several aspects of the current investigation on the CD phenomena: the emphasis is on its mechanisms and how they can be analyzed using computational methods in strong reference to the experimental data. We analyzed the mechanisms of interactions of the aromatic and disulfide chromophores mainly in the near-UV CD as the number is smaller and allows detailed analysis. We describe some of the investigations on model systems and improve the parameter sets for the approximated CD modeling methods and key calculations on several proteins. We also provide a comprehensive survey on the investigations done in our group on the chiropticity of class A β-lactamases.