Theoretical studies on structure, function and dynamics of retinal-binding proteins

Date of Completion

January 2006


Chemistry, Biochemistry|Chemistry, Physical




The structure, function and dynamics of the retinal-binding proteins, bacteriorhodopsin, 4-keto bacteriorhodopsin and rhodopsin are investigated by using theoretical methods. Retinal-binding proteins are composed of seven transmembrane helical domains and a retinylidene chromophore covalently attached to a lysine residue via a Schiff base linkage. A detailed discussion of the retinal-binding proteins is presented in Chapter one. Chapter two discusses the nature of the low frequency modes of bacteriorhodopsin (BR) and a variant, D96N. The low frequency modes are calculated by using normal mode analysis and molecular dynamics simulations. The calculated THz spectra are compared with available experimental data. A comparison of the two theoretical methods is also presented. Differences in the nature of the low frequency modes between the wild-type and D96N bacteriorhodopsin are studied as well. Chapter three focuses on the mechanisms of spectral tuning of an analog of BR, 4-keto bacteriorhodopsin. This pigment exhibits an abnormally blue-shifted absorption spectrum relative to wild-type BR. Wavelength selection in bacteriorhodopsin is affected by chromophore conformation and the interaction of the chromophore with the surrounding residues. These factors are investigated in Chapter 3 to explain the blue-shift in 4-keto BR. The energies of different models of 4-keto BR with different chromophore conformations and orientation of the Arg 82 residue are compared. Chapter four investigates the protonation states of important residues in the visual pigment, rhodopsin. This study is focused on the protonation state of Glu181, which is in the vicinity of the chromophore and is important in the activation of the protein. The pKas of the different residues are calculated by using multiconformation continuum electrostatics. ^