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 Title: Molecular dynamics studies of the protein bacteriorhodopsin Author(s): Humphrey, William Fowler Doctoral Committee Chair(s): Schulten, Klaus J. Department / Program: Physics Discipline: Physics Degree Granting Institution: University of Illinois at Urbana-Champaign Degree: Ph.D. Genre: Dissertation Subject(s): Biology, Molecular Chemistry, Biochemistry Biophysics, General Abstract: Molecular dynamics (MD) simulations are employed to study the structure and function of the protein bacteriorhodopsin (bR), a 26 kD protein which residues in the purple membrane of the bacterium Halobacterium halobium. Bacteriorhodopsin undergoes a light-driven cyclic process, which pumps protons across the membrane, in order to maintain a proton gradient necessary for ATP synthesis. The cycle is initiated through a $trans\to cis$ isomerization of the chromophore retinal, which is bound to a lysine residue via a protonated Schiff base linkage. The study of bR is facilitated through development of the program VMD for visualization of the simulation results, and the program NAMD for MD calculations on parallel computers. Initially, MD simulations are used to develop a refined three-dimensional structure of the protein, using the experimentally determined electron-microscopy structure of bR as a basis, and to determine equilibrium positions for several water molecules within the protein interior. MD simulations are then used to model the early isomerization reaction events in the bR photocycle, for both the native (wild-type) system and several bR mutants. The simulations reveal the possibility for bR to form two or three unique photoproducts, distinguished by the retinal isomeric state and the orientation of the Schiff base proton relative to nearby water molecules and negatively charged aspartic acids. One particular photoproduct is suggested to lead to successful proton pump activity, while the remaining structures return back to the initial state; this result is supported by simulations of non-functional bR mutants, which do not exhibit formation of the suggested functional photoproduct. The very fast initial retinal photoexcitation and subsequent isomerization reaction are also examined in detail using a combined quantum/classical simulation technique, in which the evolution of the density matrix for the retinal isomerization degree of freedom is computed using the Liouville-von Neumann equation. The simulations result in wild-type bR exhibiting a non-adiabatic crossing between excited states after 500 fs, while the computed excited-state lifetimes for mutants D85N and D212N are an order of magnitude longer. The results compare well with recent femtosecond spectroscopy data for these systems and demonstrate that the lifetime of the excited state is controlled by the position and slope of the first potential energy surface crossing point. Issue Date: 1996 Type: Text Language: English URI: http://hdl.handle.net/2142/22916 ISBN: 9780591199079 Rights Information: Copyright 1996 Humphrey, William Fowler Date Available in IDEALS: 2011-05-07 Identifier in Online Catalog: AAI9712317 OCLC Identifier: (UMI)AAI9712317
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