Molecular dynamics study of the 13-cis form (bR548) of bacteriorhodopsin and its photocycle

Logunov, Ilya; Humphrey, William; Schulten, Klaus; Sheves, Mordechai

doi:10.1016/s0006-3495(95)80301-2

Cited by 40 publications

(47 citation statements)

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“…A simulation model of bR 568 has been presented (Ferrand et al, 1993b) and the thermodynamic stability of internal water molecules examined (Nina et al, 1993(Nina et al, , 1995Roux et al, 1996). Recently a structure was proposed for (13,15)cis bR, and its photocycle was simulated (Logunov et al, 1995). The results of this study provided insight into why the photocycle of (13,15)cis does not pump protons; the Schiff base nitrogen points to the intracellular side after photoisomerization of retinal.…”

Section: Introductionmentioning

confidence: 89%

Simulation Analysis of the Retinal Conformational Equilibrium in Dark-Adapted Bacteriorhodopsin

Baudry

Crouzy

Roux

et al. 1999

Biophysical Journal

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In dark-adapted bacteriorhodopsin (bR) the retinal moiety populates two conformers: all-trans and (13,15)cis. Here we examine factors influencing the thermodynamic equilibrium and conformational transition between the two forms, using molecular mechanics and dynamics calculations. Adiabatic potential energy mapping indicates that whereas the twofold intrinsic torsional potentials of the C13==C14 and C15==N16 double bonds favor a sequential torsional pathway, the protein environment favors a concerted, bicycle-pedal mechanism. Which of these two pathways will actually occur in bR depends on the as yet unknown relative weight of the intrinsic and environmental effects. The free energy difference between the conformers was computed for wild-type and modified bR, using molecular dynamics simulation. In the wild-type protein the free energy of the (13,15)cis retinal form is calculated to be 1.1 kcal/mol lower than the all-trans retinal form, a value within approximately kBT of experiment. In contrast, in isolated retinal the free energy of the all-trans state is calculated to be 2.1 kcal/mol lower than (13,15)cis. The free energy differences are similar to the adiabatic potential energy differences in the various systems examined, consistent with an essentially enthalpic origin. The stabilization of the (13,15)cis form in bR relative to the isolated retinal molecule is found to originate from improved protein-protein interactions. Removing internal water molecules near the Schiff base strongly stabilizes the (13,15)cis form, whereas a double mutation that removes negative charges in the retinal pocket (Asp85 to Ala; Asp212 to Ala) has the opposite effect.

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Section: Introductionmentioning

confidence: 89%

Simulation Analysis of the Retinal Conformational Equilibrium in Dark-Adapted Bacteriorhodopsin

Baudry

Crouzy

Roux

et al. 1999

Biophysical Journal

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“…Due to low resolution, the connecting loops between the helices were not resolved. However, based on this model calculation of the molecular dynamics provided more detailed insight into the structure of the ground state (134,237,252,395) and of intermediate states (238,321,322,611,612). The contributions of molecular dynamics studies to the structure and function of BR are reviewed in reference 501.…”

Section: Structure Of Brmentioning

confidence: 99%

Bioenergetics of the Archaea

Schäfer

Engelhard

Müller³

1999

Microbiol Mol Biol Rev

264

147

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SUMMARY In the late 1970s, on the basis of rRNA phylogeny, Archaea (archaebacteria) was identified as a distinct domain of life besides Bacteria (eubacteria) and Eucarya. Though forming a separate domain, archaea display an enormous diversity of lifestyles and metabolic capabilities. Many archaeal species are adapted to extreme environments with respect to salinity, temperatures around the boiling point of water, and/or extremely alkaline or acidic pH. This has posed the challenge of studying the molecular and mechanistic bases on which these organisms can cope with such adverse conditions. This review considers our cumulative knowledge on archaeal mechanisms of primary energy conservation, in relationship to those of bacteria and eucarya. Although the universal principle of chemiosmotic energy conservation also holds for Archaea, distinct features have been discovered with respect to novel ion-transducing, membrane-residing protein complexes and the use of novel cofactors in bioenergetics of methanogenesis. From aerobically respiring archaea, unusual electron-transporting supercomplexes could be isolated and functionally resolved, and a proposal on the organization of archaeal electron transport chains has been presented. The unique functions of archaeal rhodopsins as sensory systems and as proton or chloride pumps have been elucidated on the basis of recent structural information on the atomic scale. Whereas components of methanogenesis and of phototrophic energy transduction in halobacteria appear to be unique to archaea, respiratory complexes and the ATP synthase exhibit some chimeric features with respect to their evolutionary origin. Nevertheless, archaeal ATP synthases are to be considered distinct members of this family of secondary energy transducers. A major challenge to future investigations is the development of archaeal genetic transformation systems, in order to gain access to the regulation of bioenergetic systems and to overproducers of archaeal membrane proteins as a prerequisite for their crystallization.

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“…The results are mainly related to secondary structure prediction and helix/lipid interactions and not related directly to functional considerations in the bacteriorhodopsin system. A recent simulation study of the bacteriorhodopsin trimer in an explicit bilayer environment (Edholm et al, 1995; also Jahnig and Edholm, 1992) and the studies from the Schulten group (e.g., Zhou et al, 1993;Humphrey et al, 1994;Logunov et al, 1995;Xu et al, 1995Xu et al, , 1996 should be consulted for calculations more directly related to bacteriorhodopsin function.…”

Section: Figure 10mentioning

confidence: 99%

Molecular dynamics of individual alpha-helices of bacteriorhodopsin in dimyristol phosphatidylocholine. I. Structure and dynamics

Woolf¹

1997

Biophysical Journal

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Understanding the role of the lipid bilayer in membrane protein structure and dynamics is needed for tertiary structure determination methods. However, the molecular details are not well understood. Molecular dynamics computer calculations can provide insight into these molecular details of protein:lipid interactions. This paper reports on 10 simulations of individual alpha-helices in explicit lipid bilayers. The 10 helices were selected from the bacteriorhodopsin structure as representative alpha-helical membrane folding components. The bilayer is constructed of dimyristoyl phosphatidylcholine molecules. The only major difference between simulations is the primary sequence of the alpha-helix. The results show dramatic differences in motional behavior between alpha-helices. For example, helix A has much smaller root-mean-squared deviations than does helix D. This can be understood in terms of the presence of aromatic residues at the interface for helix A that are not present in helix D. Additional motions are possible for the helices that contain proline side chains relative to other amino acids. The results thus provide insight into the types of motion and the average structures possible for helices within the bilayer setting and demonstrate the strength of molecular simulations in providing molecular details that are not directly visualized in experiments.

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Molecular dynamics study of the 13-cis form (bR548) of bacteriorhodopsin and its photocycle

Cited by 40 publications

References 50 publications

Simulation Analysis of the Retinal Conformational Equilibrium in Dark-Adapted Bacteriorhodopsin

Simulation Analysis of the Retinal Conformational Equilibrium in Dark-Adapted Bacteriorhodopsin

Bioenergetics of the Archaea

Molecular dynamics of individual alpha-helices of bacteriorhodopsin in dimyristol phosphatidylocholine. I. Structure and dynamics

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