Anion-π Interactions in Flavoproteins Involve a Substantial Charge-Transfer Component

Area of Science:

• Biochemistry
• Computational Chemistry
• Molecular Biophysics

Background:

• Anion-π interactions are known to stabilize flavoproteins.
• These interactions are crucial for regulating the flavin cofactor's redox potential.
• Traditionally, anion-π interactions are attributed solely to electrostatic forces.

Purpose of the Study:

• To investigate the nature of anion-flavin interactions.
• To determine if charge-transfer contributes to anion-flavin contacts.
• To reassess the reliability of classical simulations for flavoproteins.

Main Methods:

• Multi-approach theoretical analysis.
• Examination of charge-transfer components in anion-flavin interactions.
• Analysis of existing spectroscopic data (absorption bands).

Main Results:

• Anion-flavin interactions possess a significant charge-transfer component.
• This charge transfer is supported by observed absorption bands linked to oxidized flavin and cysteine thiolate groups.
• The interaction exhibits partial covalency.

Conclusions:

• Anion-flavin interactions are not purely electrostatic.
• The charge-transfer component implies partial covalency in these interactions.
• Classical simulations of flavoproteins may be unreliable due to this finding.