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Molecular model building studies were conducted to simulate phleomycin-bleomycin (PB) antibiotics and thus assess a hypothetical polyphleomycin-DNA complex proposed earlier. While the latter model was not conclusively proved it was found to be quite consistent with the structure of PB compounds.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
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A molecular model of the excitatory postsynaptic membrane is given in terms of two biochemical cycles intimately associated: an acetylcholine cycle and a calcium cycle. The acetylcholine controls the Na ionophores while calcium ions control the tk ionophore. The two ionophores are spatially separated but interact in such a way that the variation in K conductance precedes that in Na conductance. Digital simulation shows that our model accounts quantitatively for both the evolution of excitatory postsynaptic potential and current in a variety of experimental conditions.
Methods are presented for practicing the viewing of stereoscopic pictures of crystal structures and molecular models without optical aids.
The first simulation of the fluid mosaic model is reported. Intra-membrane particles, initially "placed" randomly in a membrane with fluid properties, are allowed to diffuse in the plane of the membrane and to interact with one another, in a model using molecular parameters. The resulting particle aggregates are very similar to those observed in freeze-fracture electron microscopy.
The structure of ribosomal 5 S RNA has been examined using several physical biochemical techniques. Hydrodynamic measurements yield a s020,omega and [eta] of 5.5 x 10(-13) x and 6.9 ml/g, respectively. Other parameters calculated from these values indicate the shape of 5 S RNA is consistent with that of a prolate ellipsoid 160 A in length and 32 A wide. Sedimentation equilibrium results show that 5 S RNA exists as a monomer in the reconstitution buffer with an apparent molecular weight of 44,000. Ultraviolet absorption difference spectra show that approximately 75% of the bases in 5 S RNA are involved in base pairing, and of these base pairs 70% are G-C and 30% are A-U. These results on the overall shape and secondary structure of 5 S RNA have been incorporated with the results of other investigators as to the possible location of single-stranded and double-stranded helical regions, and a molecular model for 5 S RNA is proposed. The molecular model consists of three double helices in the shape of a prolate ellipsoid, with two of the double helical regions at one end of the molecule. The structure is consistent with the available data on the structure and function of 5 S RNA and bears similarity to the molecular model proposed by Osterberg et al. ((1976) Eur. J. Biochem. 68, 481-487) based on small angle x-ray scattering results and the secondary structure proposed by Madison ((1968) Annu. Rev. Biochem. 37, 131-148).
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A tertiary structural model is suggested for Escherichia coli 5-S RNA that consists of one large and two small double helices arranged in the form of the letter Y. This model is consistent with the small-angle X-ray scattering data of native 5-S RNA, measured in the angular range 20 less than or equal to 140 mrad. The radium of gyration is 3.61 +- 0.1 Nm. Denatured 5-S RNA yields a much lower radius of gyration, 2.7 nm, which might indicate that during denaturation one minor double-helical arm of the Y-shaped structure partially collapses into single-stranded areas. At high concentrations (60 mg/ml) of 5-S RNA, the X-ray scattering data indicate that 5-S RNA is aggregated.
The crystal structure of pig heart citrate synthase was analyzed at 0.35-nm resolution. Chain tracing was possible and an initial molecular model constructed. The dimensions of the dimer molecule (located on a crystallographic diad) are 7.5 x 6.0 x 9.0 nm. The chain folding is characterized by the predominance of helices and the absence of sheet structure. The electron density accounts for 355 residues per monomer, so that about 80 residues must be disordered in the crystal. The disordered segment in probably N-terminal. The ordered part consists of two closely associated domains, a large domain with 300 residues and a C-terminal domain of 55 residues consisting of 3(anti)parallel helices. The large domain is built from 12 helical segments, some of which are buried in the interior of the molecule. Inhibitor binding studies with citrate and CoA revealed citrate binding sites but showed no electron density for CoA. It is suggested that CoA binds to the disordered, flexible N-terminal domain. Experiments of limited proteolysis with trypsin showed that under conditions a segment of Mr 9000 is cleaved off selectively. The remaining 35 000-Mr part is dimeric.
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The functional capabilities of the brain are formally characterizable interms of a finite system along with a memory space which it can manipulate. Two types of learning are possible: (1) modification-based learning, associated with alternate realizations of the finite system; (2) memory-based learning, associated with the assimilation, manipulation, and retrieval of memories. Constructive models which fulfill these conditions and which at the same time operate on the basis of molecular information processing principles have certain general features. We describe these features in terms of two interfaced submodels, the first for the finite system and the second for the memory space. The finite system may be realized by networks of neurons in which the specificity of enzyme molecules controls the nerve impulse. Such a realization is amenable to modification-based learning mediated by processes analogous to those of natural evolution and selective theories of antibody synthesis. The memory space is realizable by networks of neurons in which the conformation of dendritic receptor molecules controls the nerve impulse. In this case certain neurons firing in response to an external input undergo sensitization at the dendrites and in such a way that they are loadable and later callable by reference neurons, thereby allowing for reconstruction of manipulation of the firing pattern associated with this input. The overall construction makes a large number of biochemical, anatomical, physiological, and psychological predictions which are either testable or in good agreement with fact.
A molecular and biochemically plausible model for the excitation process of the sodium pore is suggested. From basic arguments it is concluded that the sodium pore exists in at least three states: the resting state, the sodium conducting state, and the refractory state. They are connected to form a cyclic process. A specification of the different states is given. It is suggested that inactivation of the sodium pore results from a conformational change, which is caused by the transport of a calcium ion through the membrane. The transport carrier is the sodium pore. This assumption can explain the observed calcium influx during stimulation, and the effect of Ca on the rate of inactivation and on the rate, at which sodium conductance shuts off upon repolarization. It cannot give a quantitative explanation for the effect of Ca on the rate of rise, peak sodium conductance, and steady state inactivation. These asects are successfully described by the surface potential hypothesis, which has been published recently. It is concluded, that a combination of both theories gives a rather complete description of the sodium pore. The Ca transport model is discussed quantitatively and in great detail.