Quantitative first principles calculations of protein circular dichroism in the near-ultraviolet

Li, Zhuo; Hirst, Jonathan D.

doi:10.1039/c7sc00586e

Cited by 35 publications

(38 citation statements)

References 98 publications

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“…The quality of the calculated near-UV CD spectra has been systematically assessed [11] over a set of 40 proteins, for which there are published experimental spectra. The correlation between the computed and the experimental intensity from 270 to 290 nm is much improved; the root mean squared error (RMSE) in the computed intensity in this wavelength range is reduced by typically a factor of two compared to the previous best calculations.…”

Section: Resultsmentioning

confidence: 99%

“…The good agreement and the sensitivity to modest structural differences motivate us to investigate the detailed interactions that govern the spectrum. The interactions of different transitions in the protein environment are computed in the exciton matrix method calculation as the purely electrostatic, Coulombic interaction energy between two transition charge densities, each represented by a set of point charges (as part of the parameter set, described in detail in our earlier work [11]). They depend on the charge densities and on their relative orientation and separation.…”

Section: Resultsmentioning

confidence: 99%

“…Vibrational structure is an important, but not the sole, contributor to the bandwidth of transitions. Extension of the approach is exactly analogous for the near-UV [11], where we have developed new parameters for the phenylalanine (Phe), tyrosine (Tyr) and tryptophan (Trp) side chains, each of which has four electronic states (L b , L a , B b , B a ) as labeled by Platt [47]. For near-UV CD spectra, the main focus of interest is the L b and L a transitions; the higher-energy B b and B a transitions occur in the far-UV [48].…”

Section: Methodsmentioning

confidence: 99%

“…We have recently [11] made some advances in the accuracy of calculations in the near-UV, realized through the consideration of the vibrational structure of the electronic transitions of aromatic side chains and significant improvements have been established over a set of diverse proteins. The conformational influences of protein structure on near-UV CD spectra are rooted in the same fundamental physical origins as those on the far-UV CD spectra, but the structural relationship is most likely rather more subtle than in the far-UV, where the regular, repeating nature of the backbone chain in well-defined secondary structures dominates.…”

Section: Introductionmentioning

confidence: 99%

“…A central component of approximate approaches for computing protein CD is the set of parameters used to model the electronic excitations of the various chromophores in proteins. Over the years, we have used ab initio quantum chemical methods to develop parameter sets that have improved the accuracy of protein CD calculations, in the vacuum-UV [8], where bands arise due to charge-transfer transitions, in the far-UV [9], where the backbone nπ* and ππ* transitions appear, and in the near-UV [10,11], where the main contribution is from the aromatic L a and L b ππ* transitions. These parameters and the computational methodology are available via our DichroCalc web interface [12] and have been used by over 1400 different researchers to compute the CD spectra of more than 3.3 million structures, including all the proteins in the Protein Data Bank (PDB) [13], models and snapshots from molecular dynamics (MD) simulations.…”

Section: Introductionmentioning

confidence: 99%

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DichroCalc: Improvements in Computing Protein Circular Dichroism Spectroscopy in the Near-Ultraviolet

Jasim

Guest

et al. 2018

Journal of Molecular Biology

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A fully quantitative theory connecting protein conformation and optical spectroscopy would facilitate deeper insights into biophysical and simulation studies of protein dynamics and folding. The web server DichroCalc (http://comp.chem.nottingham.ac.uk/dichrocalc) allows one to compute from first principles the electronic circular dichroism spectrum of a (modeled or experimental) protein structure or ensemble of structures. The regular, repeating, chiral nature of secondary structure elements leads to intense bands in the far-ultraviolet (UV). The near-UV bands are much weaker and have been challenging to compute theoretically. We report some advances in the accuracy of calculations in the near-UV, realized through the consideration of the vibrational structure of the electronic transitions of aromatic side chains. The improvements have been assessed over a set of diverse proteins. We illustrate them using bovine pancreatic trypsin inhibitor and present a new, detailed analysis of the interactions which are most important in determining the near-UV circular dichroism spectrum.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

DichroCalc: Improvements in Computing Protein Circular Dichroism Spectroscopy in the Near-Ultraviolet

Jasim

Guest

et al. 2018

Journal of Molecular Biology

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Circular Dichroism in Analysis of Biomolecules

Rodger,

Pančoška

2024

Encyclopedia of Analytical Chemistry

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Circular dichroism ( CD ) spectroscopy belongs to the family of chiroptical methods. These methods utilize the interaction of circularly polarized light ( CPL ) with chiral molecules and molecular systems to obtain information about their structure and electronic or vibrational states. A CD spectrum Δϵ(ν) is the difference of two absorbance spectra: one measured with left circularly polarized light ( LCPL ) and the other one recorded with right circularly polarized light ( RCPL ) Δϵ(ν) = ϵ L (ν)–ϵ R (ν). CD spectra can be measured as electronic circular dichroism ( ECD ) in spectral regions of electronic transitions ( ultraviolet ( UV ) and visible ( VIS ) light) and as vibrational circular dichroism ( VCD ) in the infrared ( IR ) spectral regions. An ECD spectrum for chiral fluorophores can be also recorded as the difference excitation spectrum for fluorescence spectra excited by LCPL and RCPL, respectively ( fluorescence‐detected circular dichroism ( FDCD )). Raman optical activity ( ROA ) and circularly polarized luminescence spectroscopies complete the family of currently developed chiroptical methods. The differences Δϵ(ν) measured as CD are typically ∼10 −5 of sample absorbance. Special modifications of dispersive (for ECD and VCD) or Fourier transform infrared ( FTIR ) (for VCD) spectrometers are needed to measure CD with a reasonable signal‐to‐noise ratio ( S/N ). Polarization modulation of the incident light by a photoelastic modulator and synchronous electronic processing of the resulting photoelectric signal in the spectrometers are typically used for this purpose. Molecular structure is encoded in the CD spectra because the chiral field of the CPL wave that induces a spectral transition in the chiral molecule can be observably altered both by the transition electron density redistribution (as in conventional absorption spectroscopy) and by the transition magnetic field accompanying the molecular charge redistribution. The structure and conformation of the studied molecule define the relative orientation of the characteristic directions of these two effects. This relative orientation affects the probability of absorption of photons of RCPL and LCPL and, in turn, determines the CD sign, the primary information that is unique for CD spectroscopy. In the absolute value, CD intensity (“secondary” unique information) is related to the angle of electric and magnetic transition moments and can, therefore, be converted into the molecular conformation once a suitable theoretical model is available. For complicated molecules (biomolecules, proteins, nucleic acids) where the corresponding theoretical calculations are too complex, empirical interpretive methods based on reference sets of spectra measured for molecules with known structures (from X‐ray or nuclear magnetic resonance ( NMR ) or cryo‐electron microscopy experiments) are used with success. For example, using these empirical methods, the fractions of regular secondary structures ( secondary structure fraction ( SSF )) in globular proteins can be determined with a relative error of 3–7% and the number of secondary structure segments in proteins with a typical error of one to three segments per protein fold. CD spectroscopy is highly sensitive to polarization artifacts that can be related to optical imperfections of the optical parts of the spectrometer. To achieve an acceptable S/N, the sample total absorbance A should be also controlled (typically A < 1). This, in effect, restricts the selection of usable solvents and largely determines the concentration and/or path length ranges of studied samples.

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EXAT: EXcitonic analysis tool

et al. 2017

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We introduce EXcitonic Analysis Tool (EXAT), a program able to compute optical spectra of large excitonic systems directly from the output of quantum mechanical calculations performed with the popular Gaussian 16 package. The software is able to combine in an excitonic scheme the single-chromophore properties and exciton couplings to simulate energies, coefficients, and excitonic spectra (UV-vis, CD, and LD). The effect of the environment can also be included using a Polarizable Continuum Model. EXAT also presents a simple graphical user interface, which shows on-screen both site and exciton properties. To show the potential of the method, we report two applications on a a chiral perturbed BODIPY system and DNA G-quadruplexes, respectively. The program is available online at http://molecolab.dcci.unipi.it/tools/. © 2017 Wiley Periodicals, Inc.

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Quantitative first principles calculations of protein circular dichroism in the near-ultraviolet

Abstract: Including the vibrational structure of the electronic transitions of aromatic groups allows quantitative calculation of protein near-UV circular dichroism.

Cited by 35 publications

References 98 publications

DichroCalc: Improvements in Computing Protein Circular Dichroism Spectroscopy in the Near-Ultraviolet

DichroCalc: Improvements in Computing Protein Circular Dichroism Spectroscopy in the Near-Ultraviolet

Circular Dichroism in Analysis of Biomolecules

EXAT: EXcitonic analysis tool

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