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.

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

A generalized approach combining Quantum Mechanics (QM) and Molecular Mechanics (MM) calculations is developed to simulate the n → π* and π → π* backbone transitions of proteins in aqueous solution. These transitions, which occur in the ultraviolet (UV) at 180–220 nm, provide a sensitive probe for secondary structures. The excitation Hamiltonian is constructed using high level electronic structure calculations of N-methylacetamide (NMA). Its electrostatic fluctuations are modeled using a new algorithm, EHEF, which combines a molecular dynamics (MD) trajectory obtained with a molecular mechanics forcefield, and electronic structures of sampled MD snapshots calculated by QM. The lineshapes and excitation split-tings induced by the electrostatic environment in the experimental UV linear absorption (LA) and circular dichroism (CD) spectra of several proteins in aqueous solution are reproduced by our calculations. The distinct CD features of α-helix and β-sheet protein structures are observed in the simulations and can be assigned to different backbone geometries. The fine structure of the UV spectra is accurately characterized and enables us to identify signatures of secondary structures.

Circular dichroism (CD) is widely used in the structural characterization and secondary structure determination of proteins. The vacuum UV region (below 190 nm), where charge-transfer transitions have an influence on the CD spectra, can be accessed using synchrotron radiation circular dichroism (SRCD) spectroscopy. Recently, charge-transfer transitions in a conformationally diverse set of dipeptides have been characterized ab initio using complete active space self-consistent field calculations, and the relevant charge distributions have been parametrized for use in the matrix method for calculations of protein CD. Here, we present calculations of the vacuum UV CD spectra of 71 proteins, for which experimental SRCD spectra and X-ray crystal structures are available. The theoretical spectra are calculated considering charge-transfer and side chain transitions. This significantly improves the agreement with experiment, raising the Spearman correlation coefficient between the calculated and the experimental intensity at 175 nm from 0.12 to 0.79. The influence of the conformation on charge-transfer transitions is analyzed in detail, showing that the n f π* charge-transfer transitions are most important in R-helical proteins, whereas in strand proteins the π f π* charge-transfer transition along the chain in the amino-to carboxy-end direction is most dominant.