Ligand Discrimination in Myoglobin from Linear-Scaling DFT+U

Area of Science:

• Biochemistry
• Computational Biology
• Biophysics

Background:

• Myoglobin's heme group binds diatomic molecules.
• Hydrogen-bonding and steric interactions influence ligand binding.
• Myoglobin serves as a benchmark for biomolecular computational studies.

Purpose of the Study:

• To computationally investigate myoglobin's heme binding site.
• To analyze the role of protein environment in ligand binding.
• To apply linear-scaling density functional theory (DFT) and DFT+U methods.

Main Methods:

• Linear-scaling density functional theory (DFT) calculations.
• DFT+U method to correct for self-interaction errors.
• Modeling of the myoglobin heme binding site and surrounding protein environment (>1000 atoms).

Main Results:

• Confirmed the hydrogen-bonding contribution to ligand discrimination (3.6 kcal/mol).
• Validated low protein strain energy (<1 kcal/mol).
• Demonstrated the utility of advanced computational methods for biomolecular systems.

Conclusions:

• Computational methods accurately model myoglobin's ligand binding.
• Findings support the role of specific interactions in molecular recognition.
• Expanded computational capabilities for drug design and enzymology.