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

Abstract

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.

Determination of the iron bioavailability, conformation, and rheology of iron‐binding proteins from Tegillarca granosa

“…The CD spectra of TH, BH, TF, and BF (Figure 3) showed that all proteins had positive and negative absorption peaks in the 190–202 nm and 202–250 nm wavelength ranges. These absorption peaks are characterized as α‐helix, β‐sheet, β‐turn and random coil, and shifts of these peaks reflect changes in the protein's secondary structure (Jasim et al., 2018). Table 2 shows the secondary structure composition of TH, BH, TF, and BF, respectively.…”

Electronic Circular Dichroism Spectroscopy of Proteins

“…This plot is analogous to Figure 1, as presented by Jasim and co-workers. 57 The near-UV spectrum computed using the X-ray structure underestimates the magnitude of the CD signal found in the experimental spectrum. Two NMR models, frames 3 and 5, are in much better agreement with the experimental spectra, with frame 17 having the least intense negative bands.…”

“…55 Vibrational structure is an important, but not the sole, contributor to the bandwidth of transitions. The approach is exactly analogous for the near UV, 56,57 where Li and Hirst have developed new parameters for the Phe, Tyr, and Trp side chains. For near-UV CD spectra, the main focus of interest is the 1 L b and 1 L a transitions.…”

“…56 We illustrate these aspects using the CD spectrum of BPTI, which has been calculated by Jasim and co-workers. 57 Electrostatic potentials of regions around the aromatic residues of BPTI were calculated using the Adaptive Poisson-Boltzmann Solver (APBS). 67,68 For a residue of interest, the atomic charge and radius field parameters were set to zero in the APBS input for atoms starting at the C b carbon atom to the final atom of a side chain, and a script was used to interpolate the potentials.…”

A multi-channel in situ light scattering instrument utilized for monitoring protein aggregation and liquid dense cluster formation

“…Previously, a change of the α-helical structure content of prion protein during hydrogel formation was reported [45] and for BSA a specific change of its secondary structure and folding stability was reported upon addition of PEG [46]. Near-UV CD spectroscopy generally provides a distinct tertiary structure “fingerprint”, which is specifically sensitive to aromatic amino acids and disulfide bonds [47]. BPTI consists of 58 amino acids, containing four tyrosine residues in total, three of them are part of two neighboring β-sheet regions supporting intermolecular interactions [48].…”