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Biomedical subjects

J J Hopfield

Publications and source records attributed to J J Hopfield.

12 recordsLinked to original sources
PubMed1991

Olfactory computation and object perception.

Animals that are primarily dependent on olfaction must obtain a description of the spatial location and the individual odor quality of environmental odor sources through olfaction alone. The variable nature of turbulent air flow makes such a remote sensing problem solvable if the animal can make use of the information conveyed by the fluctuation with time of the mixture of odor sources. Behavioral evidence suggests that such analysis takes place. An adaptive network can solve the essential problem, isolating the quality and intensity of the components within a mixture of several individual unknown odor sources. The network structure is an idealization of olfactory bulb circuitry. The dynamics of synapse change is essential to the computation. The synaptic variables themselves contain information needed by higher processing centers. The use of the same axons to convey intensity information and quality information requires time-coding of information. Covariation defines an individual odor source (object), and this may have a parallel in vision.

Animals↗
PubMed1989

Modeling the olfactory bulb and its neural oscillatory processings.

The olfactory bulb of mammals aids in the discrimination of odors. A mathematical model based on the bulbar anatomy and electrophysiology is described. Simulations of the highly non-linear model produce a 35-60 Hz modulated activity which is coherent across the bulb. The decision states (for the odor information) in this system can be thought of as stable cycles, rather than point stable states typical of simpler neuro-computing models. Analysis shows that a group of coupled non-linear oscillators are responsible for the oscillatory activities. The output oscillation pattern of the bulb is determined by the odor input. The model provides a framework in which to understand the transform between odor input and the bulbar output to olfactory cortex. There is significant correspondence between the model behavior and observed electrophysiology.

Computer Simulation↗
PubMed1979

Spin equilibrium and quaternary structure change in hemoglobin A. Experiments on a quantitative probe of the stereochemical mechanism of hemoglobin cooperativity.

The molecular mechanism of hemoglobin cooperativity was studied kinetically by flash photolysis on mixed-state hemoglobins which consist of three ferrous carboxy subunits and one hybrid ferric subunit including fluoromet, azidomet, cyanatomet, and thiocyanatomet. The effects of conformational transitions on the hybrid subunit were detected by kinetic absorption spectroscopy after the CO was fully photodissociated from the binding sites by a large pulse of light from a tunable dye laser. The hemoglobin conformational transition rate was observed to depend on its state of ligation. At 22 degrees C, pH 7, and 0.1 M phosphate, the deoxy R yields T conformational change rate is 4 x 10(4)s-1. The rate decreases to 1.4 x 10(4)s-1 for singly ligated hemoglobin. The R yields T conformation change alters the energy separation between high- and low-spin states for azidomet, cyanatomet, and thiocyanatomet subunits by about 700, 300, and 300 cal/mol, respectively. There are two possible implications of this result: (1) the iron atom spin state is not the only major factor in the determination of its position with respect to the heme plane or (2) the change with conformation of the protein force exerted by the proximal histidine on the iron atom (for an iron to heme-plane displacement of less than 0.3 A) is less than 50% of that expected from simple models in which this motion is responsible for cooperativity.

Azides↗
PubMed1978

Origin of the genetic code: a testable hypothesis based on tRNA structure, sequence, and kinetic proofreading.

We hypothesize that the origin of the genetic code is associated with the structure of the tRNA that existed in primal cells. The sequences of modern tRNA contain correlations which can be understood as "fossil" evidence of the secondary structure of primal tRNA. Kinetic proofreading through diffusion can amplify a low level of intrinsic selectivity of tRNA for its amino acid. Experimental tests of the theory are suggested.

Amino Acyl-tRNA Synthetases↗
PubMed1977

Photo-induced charge transfer. A critical test of the mechanism and range of biological electron transfer processes.

The vibronic coupling theory of electron tunneling between biomolecules requires that all such tunnelings involve vibronic coupling, finds temperature dependence to tunneling at finite temperatures, and predicts relatively short tunneling distances. This theory might be expected to apply to most electron transfers involved in the membrane-bound electron transfer reactions of photosynthesis and oxidative phosphorylation. This paper calculates the properties of a weak charge-transfer optical absorption band, whose predicted characteristics are a direct and simple consequence of the model that describes vibronically coupled tunneling. The new absorption band provides the basis for a critical experimental test of the constructs and parameters of the tunneling theory. If the tunneling theory is valid, the oscillator strength of such bands will be the most reliable measure of the tunneling matrix element and of the distance between the sites exchanging an electron.

Electron Transport↗
PubMed1977

Experimental test of the vibronically coupled tunneling description of biological electron transfer.

Evidence for the constructs central to vibronically coupled electron transfer has been obtained. Our experiments show the existence of a weak (f congruent to 10(-6)) charge-transfer absorption band in the near infrared for the bound donor-acceptor complex, cytochrome c-Fe(CN)6. Such a charge-transfer band had been predicted from the theory of such transfers. The experimental method, using a form of excitation modulation spectroscopy, measures only the optical absorption that induces charge transfer between the donor and the acceptor (and does not detect other absorptions) and allows the study of charge-transfer bands whose absorbances are small compared to the sample absorbance. The energy position and oscillator strength of the band agree with the general predictions of this vibronically coupled tunneling theory. We suggest that, in this system at room temperature, the electron transfer can be described by this tunneling theory. This model system result gives credence to the short electron transfer distances the theory has predicted for biological electron transfers.

Biophysical Phenomena↗
PubMed1977

Experimental evidence for kinetic proofreading in the aminoacylation of tRNA by synthetase.

The enzymatic aminoacylation of tRNA can be viewed as a means of proofreading either the amino acid or the tRNA or both. We have conducted further experimental tests of kinetic proofreading in discriminating between cognate and noncognate amino acids and tRNAs as follows: (formula: see text). In cases (i) and (ii) the amino acids are proofread, in cases (iii) and (iv) the tRNA is proofread, and in case (v), both the amino acid and the tRNA are proofread. ATP consumed per acylation was 400, 1.5, 40, 25, and 1000, respectively. High ATP/aminoacylation ratios are diagnostic for kinetic proofreading.

Amino Acyl-tRNA Synthetases↗
PubMed1977

Fundamental aspects of electron transfer: experimental verification of vibronically coupled electron tunneling.

A detailed investigation of the applicability of the vibronically coupled electron tunneling theory in biomolecules can be made by a quantitative study of a weak charge-transfer optical absorption band that has been predicted by this theory. The measurement of the position, width, and molar extinction coefficient of this band is examined in the bound model system cytochrome c-Fe(CN)6 at room temperature and demonstrates that the theory is quantitatively applicable in this system. The size of the parameters measured is typical of those relevant for biological electron transfers. The comparisons lend credibility to the generality of vibronically coupled electron theory in biomolecules and its short transfer distances.

Animals↗
PubMed1976

On electron transfer.

The tunneling transfer of electrons between two sites, appropriate to biological intermolecular electron transfer, contains physical considerations which are not important in the tunneling transfer between two metals. Analyses (such as the recent one by Hales) based on the well-known formula for the latter but applied to the former case are quantitatively and qualitatively misleading.

Electron Transport↗
PubMed1976

Rate of quaternary structure change in hemoglobin measured by modulated excitation.

Using a novel technique of modulated photo-dissociation of carbon monoxide from hemoglobin, we have obtained the rates for conversion between the two quaternary states, R, and T, at 3-fold ligation. Our measurements at pH 7 and 22 degrees give rates of 780 +/- 40 sec-1 for going from R to T, and 2500 +/- 200 sec-1 from T to R. This yields an equilibrium constant of 0.31 +/- 0.04, which is in good agreement with previous estimates. The degree of agreement between this equilibrium constant and that predicted from the allosteric model provides a new, quantitative test of the allosteric description. A sequential model for the change in structure was found incompatible with the data, even if kinetic subunit inequivalence was assumed. The technique described here is quite general and can be used as long as the system under investigation can be repetitively excited in a regime in which it responds linearly to the excitation.

Allosteric Regulation↗
PubMed1976

Direct experimental evidence for kinetic proofreading in amino acylation of tRNAIle.

Kinetic proofreading is a reaction scheme with a structure more complicated than that of Michaelis kinetics, which leads to a proofreading for errors in the recognition of a correct substrate by an enzyme. We have measured the stoichiometry between ATP hydrolysis and tRNAIle charging, using the enzyme isoleucyl-tRNA synthetase [L-isoleucine:tRNAIle ligase (AMP-forming), EC 6.1.1.5] and the amino acids isoleucine (correct) and valine (incorrect). The enzymatic deacylation of charged tRNA, which would normally prevent meaningful stoichiometry studies, was eliminated by the use of transfer factor Tu-GTP, (which binds strongly to charged tRNA) in the reaction mixture. For isoleucine, 1.5 ATP molecules are hydrolyzed per tRNA charged, but for valine, 270. These stoichiometry ratios are fundamental to kinetic proofreading, for the energy coupling is essential and proofreading is obtained only by departing from 1:1 stoichiometry between energy coupling and product formation. Within the known reaction pathway, these ratios demonstrate that kinetic proofreading induces a reduction in errors by a factor of 1/180. An overall error rate of about 10(-4) for tRNA charging is obtained by a kinetic proofreading using a fundamental discrimination level of about 10(-2), and is compatible with the low in vivo error rate of protein synthesis.

Adenosine Triphosphate↗