Density functional theory calculations of redox properties of iron–sulphur protein analogues

Abstract

A central issue in understanding redox properties of iron-sulphur (Fe-S) proteins is determining the factors that tune the reduction potentials of the Fe-S clusters. Studies of redox site analogues play an important role, particularly because individual factors can be examined independently of the environment by combining calculations and experiments of carefully designed ligands for the analogues. For iron-sulphur analogues, our study has shown that broken-symmetry density functional theory gives good energetics when the geometry is optimised using B3LYP with a double-z basis set with polarisation functions, and the energies of these geometries are calculated using B3LYP with additional diffuse functions added to the sulphurs. A comparison of our calculated energies for redox site analogues in the gas phase against electron detachment energies measured by a combination of electrospray ionisation and photoelectron spectroscopy (EI-PES) by Wang and co-workers has been essential because the comparison is for exactly the same molecule with no approximation for the environment. Overall, the correlation of our B3LYP/ 6-31(þþ) S G**//B3LYP/6-31G** detachment energies with EI-PES experiments is excellent for a wide variety of analogues. Moreover, our calculations at this level have provided insight into a wide variety of properties of iron-sulphur proteins.Dr Shuqiang Niu is a computational chemist interested in exploring complex electronic structures, physical properties, and reaction mechanisms of chemical and biological molecules using quantum mechanical and hybrid quantum mechanics/molecular mechanics methods. He received his B.S. and M.S. degrees in physical chemistry from Nankai University. After teaching for two years at Nankai University, he joined Professor R. Gleiter's group at Heidelberg University, Germany, and completed his Ph.D. degree in computational and organic chemistry in 1994. He then did postdoctoral work with Professor Michael Hall at Texas A&M University (1994 -1999) and with Dr Jeffrey Nichols at Pacific Northwest National Laboratories (1999 -2000) developing and applying computational methodologies for investigations of catalytic reactions and enzymatic mechanisms. He joined Professor Toshiko Ichiye's group at Washington State University in 2000 and then moved to Georgetown University with her in 2003. His current research primarily focuses on the simulation and prediction of redox properties of iron-sulfur proteins. Health. Her research involves computational and theoretical studies of biological macromolecules and other condensed matter systems at a molecular level. One major research interest is in understanding properties of electron transfer proteins utilising both quantum mechanical calculations of redox site analogs and classical mechanical calculations of the proteins. Another major interest is in understanding the underlying molecular basis of the unusual properties of water and in developing models of water for liquid state computer simulations using molecular multipole expansions.

Understanding Rubredoxin Redox Sites by Density Functional Theory Studies of Analogues

“…22-24 Our systematic investigations using B3LYP for [1Fe], 25,26 [2Fe-2S] 27,28,29 and [4Fe-4S] 30,31 analogues are in good agreement with PES detachment energies, while comparisons with the literature show that BP86 functional gives poorer energies. 6 Moreover, our recent studies of [4Fe-4S] proteins have shown that the reduction potentials combining Δ red G in from BS-DFT calculations of gas-phase analogues with Δ red G out from Poisson-Boltzmann (PB) continuum electrostatic calculations of protein crystal structures using partial charges for the redox site from the BS-DFT calculations are in good agreement with experiment. 32 However, these studies also show the conformational dependence of the detachment energies.…”

“…Calculations of the energetics of the reduction reaction A + e − → A − have been described thoroughly 6 and so are only summarized here. The VDE and VAE (Figure 1b), assuming that most of the coordinates are in their ground vibrational state, are calculated as $$\begin{array}{cc}right& left\mathrm{VDE}\approx \left[E_{\mathrm{elec}}^A\right(A^{-})-E_{\mathrm{elec}}^{A^{-}}(A^{-}\left)\right]+\left[E_{\mathrm{vib},0}^A\right(A)-E_{\mathrm{vib},0}^{A^{-}}(A^{-}\left)\right]\\ right& left\mathrm{VDE}\approx \left[E_{\mathrm{elec}}^{A^{-}}\right(A)-E_{\mathrm{elec}}^A(A\left)\right]+\left[E_{\mathrm{vib},0}^{A^{-}}\right(A^{-})-E_{\mathrm{vib},0}^A(A\left)\right]\end{array}$$ where E elec is the calculated electronic energy for the molecule in the superscript at the optimized geometry of the molecule in parenthesis, and E vib,0 is the calculated vibrational energy at 0 K, or ZPE.…”

Identifying sequence determinants of reduction potentials of metalloproteins

“…Details for the calculations are given elsewhere [18,19] and summarized here. The Δ G in were obtained from BS-DFT calculations at the B3LYP/6-31G(++) S **//B3LYP/6-31G** (energy calculation functional/basis set//geometry optimization functional/basis set) of Fe 4 S 4 (SCH 3 ) 4 1-/2-/3- using the program NWChem [39].…”

“…The accuracy of this DFT+PB approach is based in part on our extensive testing of the hybrid (rather than LDA) functionals and basis sets [19] used in the BS-DFT calculation of the analog against electrospray ionization - photoelectron spectroscopy (EI-PES) data [20–22] of the same analogs in the gas phase. Our DFT calculations also confirm that Δ G in for the iron-sulfur clusters is relatively independent of environment [19].…”

“…The accuracy of this DFT+PB approach is based in part on our extensive testing of the hybrid (rather than LDA) functionals and basis sets [19] used in the BS-DFT calculation of the analog against electrospray ionization - photoelectron spectroscopy (EI-PES) data [20–22] of the same analogs in the gas phase. Our DFT calculations also confirm that Δ G in for the iron-sulfur clusters is relatively independent of environment [19]. In addition, the overall DFT+PB approach has been shown to be accurate for [4Fe4S] proteins with errors of less than 50 mV for crystal structure that are at least 1.5 Å or better [1], which is a significant improvement over earlier work that calculated relative values of E ° using the PDLD or MD-PDLD methods that had errors of ~370 and ~150 mV, respectively [9].…”