Molecular Dynamics Study of Bacteriorhodopsin and Artificial Pigments

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

doi:10.1021/bi00178a025

Cited by 112 publications

(134 citation statements)

References 74 publications

(123 reference statements)

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“…23 All the simulation results were represented using Visual Molecular Dynamics (VMD) soware, version 1.9. 24 …”

Section: Model and Methodsmentioning

confidence: 99%

Molecular analysis of interactions between dendrimers and asymmetric membranes at different transport stages

et al. 2014

Soft Matter

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Studying dendrimer-biomembrane interactions is important for understanding drug and gene delivery. In this study, coarse-grained molecular dynamics simulations were performed to investigate the behaviors of polyamidoamine (PAMAM) dendrimers (G4 and G5) as they interacted with asymmetric membranes from different sides of the bilayer, thus mimicking different dendrimer transport stages. The G4 dendrimer could insert into the membrane during an equilibrated state, and the G5 dendrimer could induce pore formation in the membrane when the dendrimers interacted with the outer side (outer interactions) of an asymmetric membrane [with 10% dipalmitoyl phosphatidylserine (DPPS) in the inner leaflet of the membrane]. During the interaction with the inner side of the asymmetric membrane (inner interactions), the G4 and G5 dendrimers only adsorbed onto the membrane. As the membrane asymmetry increased (e.g., increased DPPS percentage in the inner leaflet of the membrane), the G4 and G5 dendrimers penetrated deeper into the membrane during the outer interactions and the G4 and G5 dendrimers were adsorbed more tightly onto the membrane for the inner interactions. When the DPPS content reached 50%, the G4 dendrimer could completely penetrate through the membrane from the outer side to the inner side. Our study provides molecular understanding and reference information about different dendrimer transport stages during drug and gene delivery.

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“…23 All the simulation results were represented using Visual Molecular Dynamics (VMD) soware, version 1.9. 24 …”

Section: Model and Methodsmentioning

confidence: 99%

Molecular analysis of interactions between dendrimers and asymmetric membranes at different transport stages

et al. 2014

Soft Matter

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“…There is experimental evidence for internal bound water in bR (34)(35)(36)(37). Molecular dynamics calculations on the bR structural model proposed by Henderson et at (13) orient a chain of water molecules just between D96 and the Schiff base as presented in the scheme (38,39).…”

Section: Methodsmentioning

confidence: 99%

Experimental evidence for hydrogen-bonded network proton transfer in bacteriorhodopsin shown by Fourier-transform infrared spectroscopy using azide as catalyst.

Coutre

Tittor

Oesterhelt

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

107

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Experimental evidence for proton transfer via a hydrogen-bonded network in a membrane protein is presented. Bacteriorhodopsin's proton transfer mechanism on the proton uptake pathway between Asp-96 and the Schiff base in the M-to-N transition was determined. The slowdown of this transfer by removal of the proton donor in the Asn mutant can be accelerated again by addition of small weak acid anions such as azide. Fourier-transform infrared experiments show in the Asp-96 -k Asn mutant a transient protonation of azide bound to the protein in the M-to-N transition and, due to the addition of azide, restoration of the IR continuum band changes as seen in wild-type bR during proton pumping. The continuum band changes indicate fast proton transfer on the uptake pathway in a hydrogen-bonded network for wild-type bR and the Asp-96 Asn mutant with azide. Since azide is able to catalyze proton transfer steps also in several kinetically defective bR mutants and in other membrane proteins, our finding might point to a general element of proton transfer mechanisms in proteins.The retinal protein bacteriorhodopsin (bR), probably the best understood example of an ion pump, is a suitable system to study intramolecular proton transfer in proteins (1). Crucial events for the transport mechanism during the photocycle via the intermediates J, K, L, M, N, and 0 are the light-induced isomerization of all-trans-retinal to 13-cis-retinal in the BRto-J photoreaction (where BR is the ground state of the bR molecule), the deprotonation of the Schiff base which is the binding site between chromophore and protein, (2-4), and protonation changes of internal aspartic acids (5). Fouriertransform infrared (FTIR) spectroscopy of mutant bRs identified the proton acceptor on the proton release pathway as Asp-85 (D85) (6-8) and the proton donor on the proton uptake pathway as D96 (8). The proton acceptor D85 is protonated in the L-to-M reaction, in which the Schiff base becomes deprotonated, whereas the donor D96 is deprotonated in the M-to-N transition, in which the Schiff base is reprotonated (9). Evidence for the catalytic role of these aspartic acids is contributed.by electrical charge displacement measurements showing disturbed proton transport in D85X and D96X mutants (10, 11). These results on the reaction mechanism were strongly confirmed in all details in a series of succeeding publications (for review, see ref. 12). The atomic structural model of bR as developed from high-resolution electron microscopic studies proposed the positions of D85 and D96 on either side of the retinal (13). Therefore they are correctly located for their role in the vectorial proton translocation process.However, the donor, D96, is positioned in the structural model about 12 A from the acceptor, the Schiff base (13). Even though the resolution of the structure in the cross section of the The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S...

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“…In our study, the refined structure of bacteriorhodopsin reported in [31] was used as a starting point for all the computations. This structure, corresponding to the bR 568 pigment, is depicted in Figures 2a and 5b.…”

Section: Quantum Chemistry Of In Situ Retinalmentioning

confidence: 99%

“…It has been observed that modification of protein groups in the vicinity of the retinal Schiff base shifts considerably the bR absorption spectrum [69] and affects drastically the rates of both thermally- [70] and photo- [71,72] [75,76,77]. At present, there exist a number of ab initio as well as semi-empirical techniques which try to account for the realistic atomic structure and charge distribution of the environment via explicit incorporation of protein (or solution) point charges in the electronic Hamiltonian of the quantum chemically treated substrate [78,79,80,81,82,83].In our study, the refined structure of bacteriorhodopsin reported in [31] was used as a starting point for all the computations. This structure, corresponding to the bR 568 pigment, is depicted in Figures 2a and 5b.…”

mentioning

confidence: 99%

“…This structure provided an opportunity to explore, by means of computer simulations, the mechanism of bR's light-driven proton pump at the atomic level. Molecular dynamics techniques have been widely used to refine the Henderson structure and to study structural properties of the bR 568 pigment and its photocycle intermediates [29,30,31,32,33,34,35].…”

Section: Introductionmentioning

confidence: 99%

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Quantum Chemistry of in situ Retinal: Study of the Spectral Properties and Dark Adaptation of Bacteriorhodopsin

Logunov

Schulten

1996

Quantum Mechanical Simulation Methods for Studying Biological Systems

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1A combination of molecular dynamics and quantum chemistry techniques have been employed to study the electronic excitation and conformational potential surface of retinal in the binding site of bacteriorhodopsin (bR). The CASSCF(6,9)/6-31G level of ab initio calculations (within Gaussian92) has been used for the treatment of both the ground (S0) and excited (S1) states of retinal. Charges of all atoms in the protein are represented by spherical Gaussians and explicitly included in the electronic Hamiltonian of retinal. Spectral properties have been analyzed for the native bR pigment as well as for its D85N mutant.The calculated relative shift in the absorption maxima between the two pigments is in better agreement with experiment than the computed absolute parameters of the absorption line shapes. The dark adaptation processes in bacteriorhodopsin (which involves rotation around the 13-14 and the 15-N retinal double bonds) has been modelled by following the pre-defined reaction coordinate. Our simulations support the notion that the isomerization process is catalyzed by the protonation of an aspartic acid (Asp85) side group of bacteriorhodopsin. 2 IntroductionBacteriorhodopsin (bR) spans the cell membrane of Halobacterium halobium and functions as a light-driven proton pump. bR contains seven α-helices which enclose the prosthetic group, all-trans retinal, bound via a protonated Schiff base linkage to Lys-216. Figure 1a shows the chemical structure of retinal and its conventional numbering scheme. The bR structure is presented in Fig. 2a. Retinal absorbs light and undergoes a photoisomerization process; the thermal reversal of this reaction is coupled to transfer of a proton from the cytoplasmic side (top in Fig. 2a) to the extracellular side (bottom in Fig. 2a) of the protein.Recent reviews that discuss the structure and function of bR are [1,2,3,4,5,6,7]. Figure 1 here Bacteriorhodopsin accomplishes its function through a cyclic process initiated by absorption of a photon. This photon triggers an isomerization of retinal, which proceeds then through several intermediate states identified by their absorption spectra. An accepted kinetic scheme for this cycle is an unbranched series of intermediates, shown in Fig. 3. Photoisomerization occurs in the bR 568 → J 625 transition. During the L 550 → M 412 transition the Schiff base proton is transferred to Asp-85 and, subsequently, to the outside of the cell [8,9,10,11,12,13]. During the M 412 → N 520 transition, a proton is transferred to the Schiff base from Asp-96, which then takes up a proton from the cytoplasmic environment [13]. The reaction cycle is completed as the protein returns to bR 568 via the O 640 intermediate. Figure 2 here When bR is allowed to equilibrate in the dark, it converts within an hour to a 2:1 mixture containing 13-cis retinal and all-trans retinal bR [14]. The protein containing the 13-cis retinal isomer of bRis referred to as the dark adapted (DA) pigment of bR, bR 548 , which absorbs at 548 nm. bR 548 contains, actually, retinal in a 1...

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Molecular Dynamics Study of Bacteriorhodopsin and Artificial Pigments

Cited by 112 publications

References 74 publications

Molecular analysis of interactions between dendrimers and asymmetric membranes at different transport stages

Molecular analysis of interactions between dendrimers and asymmetric membranes at different transport stages

Experimental evidence for hydrogen-bonded network proton transfer in bacteriorhodopsin shown by Fourier-transform infrared spectroscopy using azide as catalyst.

Quantum Chemistry of in situ Retinal: Study of the Spectral Properties and Dark Adaptation of Bacteriorhodopsin

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