Computational Study of the Structure and Electronic Circular Dichroism Spectroscopy of Blue Copper Proteins

Abstract

The calculation of the electronic circular dichroism (CD) spectra of the oxidised form of the blue copper proteins plastocyanin and cucumber basic protein and the relationship between the observed spectral features and the structure of the active site of the protein is investigated.Excitation energies and transition strengths are computed using multi reference configuration interaction, and it is shown that computed spectra based on coordinates from the crystal structure or a single structure optimised in quantum mechanics/molecular mechanics (QM/MM) or ligand field molecular mechanics (LFMM) are qualitatively incorrect. In particular, the rotational strength of the ligand to metal charge transfer band is predicted to be too small or have the incorrect sign. By considering calculations on active site models with modified structures it is shown that the intensity of this band is sensitive to the non-planarity of the histidine and cysteine ligands coordinated to copper. Calculation of the ultraviolet absorption and CD spectra based upon averaging over many structures drawn from a LFMM molecular dynamics simulation are in good agreement with experiment, and superior to analogous calculations based upon structures from a classical molecular dynamics simulation. This provides evidence that the LFMM force field provides an accurate description of the molecular dynamics of these proteins.

A QM/MM study of the nature of the entatic state in plastocyanin

“…In this state, the protein has a rich spectroscopy, and has been studied by several different spectroscopic techniques including electronic absorption, circular dichroism, magnetic circular dichroism, and x‐ray absorption spectroscopies . Alongside these experimental measurements there have been numerous theoretical studies with a wide variety of different levels of approximation . These studies have led to an understanding of the nature of the observed spectroscopic features and detailed insight into the electronic structure of the active site.…”

“…The studies of the strain energy and the reorganization energy have been largely based on a static view of the structures. It is known that conformational averaging is important in determining the properties of these proteins . In this article, we develop a more dynamic picture of the electron transfer process.…”

“…Previous work has studied photoinduced electron transfer dynamics between the oxidized ground state and optically excited LMCT state based on classical molecular dynamics (MD) simulations . The parameterization of classical force fields to accurately describe the structure of the active site is problematic, and a previous study has shown that electronic absorption and circular dichroism spectra computed from structures from a classical MD trajectory were in poor agreement with experiment compared with those based on structures from a LFMM‐based MD simulation . QM/MM approaches have the potential to provide a more accurate and balanced treatment of the oxidized and reduced forms of the protein.…”

“…[11,12] Alongside these experimental measurements there have been numerous theoretical studies with a wide variety of different levels of approximation. [7,[13][14][15][16][17][18][19][20][21][22][23][24] These studies have led to an understanding of the nature of the observed spectroscopic features and detailed insight into the electronic structure of the active site. For example, the absorption spectrum shows peaks at 16,700 cm 21 and 12,800 cm 21 , which are assigned to a Cys(p) !…”

“…It is known that conformational averaging is important in determining the properties of these proteins. [16,23] In this article, we develop a more dynamic picture of the electron transfer process. Previous work has studied photoinduced electron transfer dynamics between the oxidized ground state and optically excited LMCT state based on classical molecular dynamics (MD) simulations.…”