Department of Chemistry, University of Kurdistan, P.O.Box 66175-416, Sanandaj, Iran.
Department of Theoretical Chemistry, Lund University, P.O.Box 124, 221 00, Lund, Sweden.
Sci Rep. 2023 Jul 4;13(1):10832. doi: 10.1038/s41598-023-37755-0.
[4Fe-4S] clusters are essential cofactors in many proteins involved in biological redox-active processes. Density functional theory (DFT) methods are widely used to study these clusters. Previous investigations have indicated that there exist two local minima for these clusters in proteins. We perform a detailed study of these minima in five proteins and two oxidation states, using combined quantum mechanical and molecular mechanical (QM/MM) methods. We show that one local minimum (L state) has longer Fe-Fe distances than the other (S state), and that the L state is more stable for all cases studied. We also show that some DFT methods may only obtain the L state, while others may obtain both states. Our work provides new insights into the structural diversity and stability of [4Fe-4S] clusters in proteins, and highlights the importance of reliable DFT methods and geometry optimization. We recommend rSCAN for optimizing [4Fe-4S] clusters in proteins, which gives the most accurate structures for the five proteins studied.
[4Fe-4S]簇是许多参与生物氧化还原过程的蛋白质中必不可少的辅助因子。密度泛函理论（DFT）方法被广泛用于研究这些簇。先前的研究表明，这些簇在蛋白质中有两个局部最小值。我们使用组合量子力学和分子力学（QM/MM）方法对五种蛋白质和两种氧化态下的这些最小值进行了详细研究。我们表明，一个局部最小值（L 态）的 Fe-Fe 距离比另一个（S 态）长，并且在所有研究的情况下，L 态更稳定。我们还表明，一些 DFT 方法可能只能获得 L 态，而其他方法可能会获得两种状态。我们的工作为蛋白质中 [4Fe-4S]簇的结构多样性和稳定性提供了新的见解，并强调了可靠的 DFT 方法和几何优化的重要性。我们推荐 rSCAN 用于优化蛋白质中的 [4Fe-4S]簇，它为研究的五种蛋白质提供了最准确的结构。
