Electronic circular dichroism of fluorescent proteins: a computational study

Area of Science:

• Computational Chemistry
• Biophysics
• Spectroscopy

Background:

• Fluorescent proteins (FPs) are crucial in biological research.
• Understanding their electronic circular dichroism (ECD) provides insights into their structure-function relationship.
• Accurate theoretical modeling of ECD is essential for interpreting experimental data.

Purpose of the Study:

• To calculate the ECD properties of green fluorescent protein and other FPs.
• To investigate the impact of various embedding models on the ECD signal.
• To identify an accurate and efficient computational approach for FP ECD calculations.

Main Methods:

• Density functional theory (DFT) calculations.
• Comparison of four embedding models: QM/PCM, PE-QM/MM, QM/QM, and QM/QM/PCM.
• Analysis of rotatory strength and oscillatory strength.

Main Results:

• Rotatory strength is more sensitive to chromophore geometry and embedding models than oscillatory strength.
• Explicit protein embedding (PE-QM/MM, QM/QM) enhances rotatory strength.
• Polarizable embedding (PE-QM/MM) is an affordable method yielding correct rotatory strength signs for all FPs.

Conclusions:

• Explicit embedding models are superior to continuum models for FP ECD.
• Polarizable embedding offers a good balance of accuracy and computational cost.
• Accurate ECD calculations are vital for understanding FP photophysics.