Two local minima for structures of [4Fe-4S] clusters obtained with density functional theory methods

Area of Science:

• Biochemistry and Biophysics
• Computational Chemistry

Background:

• Iron-sulfur clusters, specifically [4Fe-4S] clusters, are vital cofactors in biological redox reactions.
• Computational methods, particularly Density Functional Theory (DFT), are crucial for studying the structure and dynamics of these clusters.
• Prior research suggests the existence of multiple stable configurations (local minima) for [4Fe-4S] clusters within proteins.

Purpose of the Study:

• To investigate the structural diversity and relative stability of [4Fe-4S] cluster local minima in proteins.
• To evaluate the performance of different DFT methods in accurately predicting these cluster structures.
• To identify the most reliable computational approach for optimizing [4Fe-4S] cluster geometries.

Main Methods:

• Employed combined quantum mechanics/molecular mechanics (QM/MM) methods for detailed computational analysis.
• Studied five distinct proteins containing [4Fe-4S] clusters across two oxidation states.
• Systematically compared the geometries and energies of identified local minima.

Main Results:

• Identified two distinct local minima: an 'L state' with longer Fe-Fe distances and an 'S state' with shorter distances.
• Consistently found the L state to be more energetically stable across all studied proteins and oxidation states.
• Observed that certain DFT functionals predominantly locate the L state, while others can identify both L and S states.

Conclusions:

• The L state represents the more stable conformation of [4Fe-4S] clusters in the studied proteins.
• The choice of DFT functional significantly impacts the ability to capture the full structural landscape of these clusters.
• The r2SCAN functional is recommended for accurate geometry optimization of [4Fe-4S] clusters in proteins due to its superior performance in the studied cases.