Proteins have characteristic circular dichroism spectra in the far-ultraviolet, depending on their secondary structure content. Perhaps the most distinctive spectrum is that of α-helical proteins, with an intense positive band centered about 190 nm and a negative, double-peaked band with minima at 208 and 220 nm. Traditionally, calculations of such spectra from first principles have involved parametrizations of the charge distributions associated with the electronic states and transitions of the constituent chromophoric groups. The amide group is the most important of these chromophores. In this study, using solution phase ab initio parametrizations of the amide chromophore, we present first-principles calculations of protein circular dichroism. Over a set of 29 proteins, there is a significant correlation between the calculated and measured intensities at 190, 208, and 220 nm. The agreement is highest at 220 nm, with a Spearman rank correlation coefficient of 0.90. This near-quantitative accuracy has allowed us to investigate, with some confidence, the dependence of the intensity at 220 nm on helix length and backbone conformation for a number of real and model helices. In this study, a better understanding of the electronic structure of amides and improved calculations and parametrizations of the relevant charge distributions has led to significantly more accurate protein circular dichroism calculations.

In this paper different floating oscillator models for describing the amide I band of peptides and proteins are compared with density functional theory (DFT) calculations. Models for the variation of the frequency shifts of the oscillators and the nearest-neighbor coupling between them with respect to conformation are constructed from DFT normal mode calculations on N-acetyl-glycine-N′-methylamide. The calculated frequencies are compared with those obtained from existing electrostatic models. Furthermore, a new transition charge coupling model is presented. We suggest a model which combines the nearest-neighbor maps with long-range interactions accounted for using the new transition charge model and an existing electrostatic map for long-range interaction frequency shifts. This model and others, which account for the frequency shifts by electrostatic maps exclusively, are tested by comparing the predicted IR spectra with those from DFT calculations on the pentapeptide [Leu]-enkephalin. The new model described above gives the best agreement and, after a systematic blueshift is accounted for, reproduces the DFT frequencies to within 3.5cm−1. The correlation of the intensities for this model with intensities from DFT calculations is 0.94.

Circular dichroism (CD) is an important technique in the structural characterisation of proteins, and especially for secondary structure determination. The CD of proteins can be calculated from first principles using the so-called matrix method, with an accuracy which is almost quantitative for helical proteins. Thus, for proteins of unknown structure, CD calculations and experimental data can be used in conjunction to aid structure analysis. Linear dichroism (LD) can be calculated using analogous methodology and has been used to establish the relative orientations of subunits in proteins and protein orientation in an environment such as a membrane. However, simple analysis of LD data is not possible, due to overlapping transitions. So coupling the calculations and experiment is an important strategy. In this paper, the use of LD for the determination of protein orientation and how these data can be interpreted with the aid of calculations, are discussed. We review methods for the calculation of CD spectra, focusing on semiempirical and ab initio parameter sets used in the matrix method. Lastly, a new web interface for online CD and LD calculation is presented.

Background: Post translational modifications (PTMs) occur in the vast majority of proteins and are essential for function. Prediction of the sequence location of PTMs enhances the functional characterisation of proteins. Glycosylation is one type of PTM, and is implicated in protein folding, transport and function.

http://comp.chem.nottingham.ac.uk/dichrocalc and http://comp.chem.nottingham.ac.uk/parsepdb.