Systems Biology CASSMAN, MARVIN; ARKIN, ADAM; DOYLE, FRANK ...
2007, 2007-01-17
eBook
This book explores Systems Biology as the understanding of biological network behaviors, and in particular their dynamic aspects, which requires the utilization of mathematical modeling tightly ...linked to experiment. A variety of approaches are discussed here: the identification and validation of networks, the creation of appropriate datasets, the development of tools for data acquisition and software development, and the use of modeling and simulation software in close concert with experiment.
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For the past half-century, biologists have been uncovering details of countless molecular events. Linking these data to dynamic models requires new software and data standards, argue Marvin Cassman ...and his colleagues.
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Ruth L. Kirschstein (1926–2009) Schachman, Howard K.; Cassman, Marvin
Science (American Association for the Advancement of Science),
11/2009, Volume:
326, Issue:
5955
Journal Article
Peer reviewed
The leadership, political skills, and commitment of the first woman director at the U.S. National Institutes of Health are unrivaled.
In a discussion about the U.S. National Institutes of Health ...(NIH) several years ago, Ruth Kirschstein commented, “I love it.” And it showed. She served with distinction in countless positions and her imprint is evident in virtually all NIH policies and practices. With her passing last month from cancer, the world has lost a creative and dedicated public servant.
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4.
Retrospective: Ruth L. Kirschstein (1926-2009) Schachman, Howard K.; Cassman, Marvin
Science (American Association for the Advancement of Science),
2009-Nov-13, Volume:
326, Issue:
5955
Journal Article
Peer reviewed
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5.
Counting on the Neuron Cassman, Marvin
Science (American Association for the Advancement of Science),
05/2003, Volume:
300, Issue:
5620
Journal Article
Peer reviewed
The traditional application of computational methods to cell and molecular biology has been in the arena of computational chemistry. More recently, computational genomics and bioinformatics have ...emerged from the sequencing of the genomes of many different organisms.
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6.
Beef Heart Malic Dehydrogenases Cassman, Marvin
The Journal of biological chemistry,
05/1967, Volume:
242, Issue:
9
Journal Article
Peer reviewed
Open access
The constants for the dissociation of reduced diphosphopyridine nucleotide from both the binary ( E . DPNH) and ternary ( E . DPNH . d -malate) complexes of bovine heart supernatant malic ...dehydrogenase have been determined at pH values between 6 and 10 by spectrofluorometric
techniques. The constants have minimum values at pH 6.5. Above pH 7, the presence of d -malate stabilizes bound DPNH. Furthermore, the dissociation constant of the binary complex increases at pH values above 9.0,
although this is not observed for the ternary complex dissociation constant. The changes are interpreted as reflecting the
titration of groups on the protein involved in the binding of DPNH.
By use of similar techniques, the dissociation constant of the ternary complex with respect to D-malate has been measured.
This constant is unchanged beween pH 6 and 8, but increases above pH 8. A group on the protein dissociating at pH 9.0 to 9.5
is considered to be involved in the binding of d -malate.
Measurements of the quantum yields of fluorescence of DPNH in the binary and ternary complexes have been made between pH 6
and pH 10. No change in the quantum yield of the free protein can be observed in the pH range from 6 to 10. The results indicate
that the quantum yield of DPNH in the complexes cannot be simply related to its dissociation constant. Some of the effect
of d -malate on the DPNH quantum yield is attributed to local electronic interactions at the DPNH-binding site, producing changes
in coenzyme fluorescence independent of changes in the stability of the bound DPNH.
A parameter, q , which defines some properties of the energy transfer phenomenon is derived. In agreement with theoretical predictions, the
energy transfer appears to be mainly nonradiative in nature. Examination of the q values indicates that a transition occurs between pH 7.0 and 7.5. A similar transition is observed with the ternary complex.
The extent of quenching of the protein fluorescence upon binding of DPNH or DPNH + d -malate has also been measured. The degree of quenching, measured between pH 7.5 and 10.0, reflects the efficiency of energy
transfer. In this pH region, the efficiency of energy transfer for both binary and ternary complexes decreases by 40 to 50%
with increasing pH. The efficiency of energy transfer is about 10% greater in the ternary than in the binary complex. Below
pH 7.5 the observed quenching is a reflection both of the energy transfer process and of quenching arising from other mechanisms.
Optical rotatory dispersion studies of free supernatant malic dehydrogenase at pH 6.5 and 8.5, and of enzyme bound to DPNH
at pH 8.5, gave almost identical b 0 values. However, measurements carried out at pH 6.5 with the enzyme-DPNH complex show a 60% increase in b 0 above the value obtained for this complex at pH 8.5.
The pH- and DPNH-dependent transition observed from optical rotation and fluorescence studies may be related to a change in
the kinetic properties of the enzyme (described in an earlier publication), which occurs over the same pH range.
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Computational biology. Counting on the neuron Cassman, Marvin
Science (American Association for the Advancement of Science),
2003-May-02, 20030502, Volume:
300, Issue:
5620
Journal Article
Peer reviewed
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8.
Beef Heart Malic Dehydrogenases Cassman, Marvin; Englard, Sasha
The Journal of biological chemistry,
02/1966, Volume:
241, Issue:
4
Journal Article
Peer reviewed
Open access
The stoichiometry of reduced diphosphopyridine nucleotide binding to supernatant malic dehydrogenase (S-MDH) was determined
by fluorometric techniques and a Sephadex gel filtration procedure. Both ...types of measurement yielded a stoichiometry of 1
mole of DPNH bound per mole of enzyme. This stoichiometry was unaffected by the presence of d -malate, a compound which is known to form a ternary enzyme complex having distinctive fluorescent properties.
The dissociation constants for the binary enzyme-DPNH and ternary enzyme-DPNH- d -malate complexes with respect to DPNH were determined.
Several criteria were used to determine the effectiveness of a number of compounds in forming ternary complexes with S-MDH
and DPNH. A requisite for ternary complex formation was a dicarboxylic acid with chain length of 3 to 4 carbon atoms. Although
an α-hydroxyl group was not necessary for ternary complex formation, the introduction of such a group in a specific steric
configuration resulted in a loss of capacity to form such a complex. Formation of strong fluorescing complexes by a number
of dicarboxylic acids is not necessarily related to their effectiveness as inhibitors of S-MDH activity. The presence of an
α-hydroxyl group appears to be required for inhibition, although added steric considerations involving the β carbon atom may
obliterate such inhibitory capacity.
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Beef Heart Malic Dehydrogenases Cassman, Marvin; Englard, Sasha
The Journal of biological chemistry,
02/1966, Volume:
241, Issue:
4
Journal Article
Peer reviewed
Open access
Kinetic studies on beef heart supernatant malic dehydrogenase were carried out in 0.1 m triethanolamine-acetate buffer. Analysis of the data by the method of Dalziel revealed that specific ...relationships between
calculated kinetic parameters did not conform to the criteria proposed for mechanisms involving sequential addition for each
pair of substrates. The results also did not conform to the criteria proposed for a mechanism involving a random order of
substrate addition to enzyme, in which all of the complexes are in rapid equilibrium with the substrates. These observations
can be contrasted with those of Raval and Wolfe (1) on hog heart malic dehydrogenase. With this enzyme, of apparent mitochondrial
origin, the results were found to be compatible with a mechanism involving an ordered addition of substrate to the enzyme,
with no kinetically active ternary complexes.
A kinetic mechanism for supernatant malic dehydrogenase has been proposed; it involves the participation of three binary complexes
of substrate and enzyme (enzyme-oxaloacetate, enzyme-diphosphopyridine nucleotide, and enzyme-DPNH) and no kinetically significant
ternary complexes. It has further been proposed that the preferred route of the reaction is via the branch of the pathway
involving enzyme-DPNH, and that the rate constants are identical for DPNH interacting either with free enzyme or with the
enzyme-oxaloacetate complex. This formulation is consistent with the experimentally determined kinetic parameters and with
the independently determined dissociation constant for enzyme-DPNH obtained by fluorometric measurements.
Substrate inhibition of supernatant malic dehydrogenase by oxaloacetate was observed at pH values below 7.8. This observation
may be interpreted as further indication of the existence of a binary enzyme-oxaloacetate complex. However, the possibility
that the inhibition is due to the formation of inactive ternary complexes with oxaloacetate cannot be ruled out.
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