Quantitative first principles calculations of protein circular dichroism in the near-ultraviolet
نویسندگان
چکیده
Vibrational structure in the near-UV circular dichroism (CD) spectra of proteins is an important source of information on protein conformation and can be exploited to study structure and folding. A fully quantitative theory of the relationship between protein conformation and optical spectroscopy would facilitate deeper interpretation of and insight into biophysical and simulation studies of protein dynamics and folding. We have developed new models of the aromatic side chain chromophores toluene, p-cresol and 3-methylindole, which incorporate ab initio calculations of the Franck–Condon effect into first principles calculations of CD using an exciton approach. The near-UV CD spectra of 40 proteins are calculated with the new parameter set and the correlation between the computed and the experimental intensity from 270 to 290 nm is much improved. The contribution of individual chromophores to the CD spectra has been calculated for several mutants and in many cases helps rationalize changes in their experimental spectra. Considering conformational flexibility by using families of NMR structures leads to further improvements for some proteins and illustrates an informative level of sensitivity to side chain conformation. In several cases, the near-UV CD calculations can distinguish the native protein structure from a set of computer-generated misfolded decoy structures.
منابع مشابه
Quantitative first principles calculations of protein circular dichroism in the near-ultraviolet† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc00586e Click here for additional data file. Click here for additional data file.
متن کامل
In vitro study of drug-protein interaction using electronic absorption, fluorescence, and circular dichroism spectroscopy
In the near future, design of a new generation of drugs targeting proteins will be required. Considering the complex bond between the drug and protein, the structure and stability of the target protein should be considered. So far, a series of in vitro investigations have been conducted with the aim of predicting drug-biological medium interactions. In these studies, use of spectroscopic method...
متن کاملFirst-principles calculations of protein circular dichroism in the near ultraviolet.
Electronic transitions in aromatic side chains are responsible for the characteristics of proteins in the near UV. We present the first systematic study of a large number of proteins focused on the accurate calculation of near-UV circular dichroism (CD) spectra. We report new parameter sets derived from ab initio calculations for benzene, phenol, and indole that describe the valence electronic ...
متن کاملVacuum ultraviolet circular dichroism as an indicator of helical handedness in nucleic acids.
Calculated circular dichroism spectra are presented for double-stranded polynucleotides of regular sequences in A-RNA, A-DNA, B-DNA, and Z-DNA conformations. Quantum mechanical matrix method calculations were carried out in the near and vacuum ultraviolet regions. In the near UV, the calculated spectra agreed qualitatively with the measured spectra. However in the far and vacuum UV, the calcula...
متن کاملMagnetic circular dichroism in the L2,3 x-ray fluorescence of Fe and Co
the L2,3 x-ray fluorescence spectra of magnetized Fe and CO excited by circularly polarized synchrotron radiation exhibit magnetic circular dichroism. The results are compared to the energy resolved spin polarized densities of states given by first-principles calculations.
متن کامل