Steve Koch

Urey, Brickwedde, and Murphy. According to Lewis & Macdonald in 1933, this paper marked the discovery of deuterium. - Steve Koch

Lewis writes, "Sir: Even before I had succeeded in concentrating the isotope of hydrogen, I predicted that H2H2O [D2O] would not support life and would be lethal to higher organisms. As soon as heavy water became available experiments to test this idea were begun, but it was necessary to choose an experiment which would require the minimum of biological technique and also very small quantities of water. The minute seeds of tobacco..." - Steve Koch

Every Lewis paper I have read in the past couple months is fantastic. This is a short but sweet paper that really has me excited about my kids' upcoming science fairs in a few years. - Steve Koch

Cute paper, kind of amusing this was realized so early, and it is still a surprise now to many people (including myself). I wonder how he made that prediction. - mkz

From Johnathan Eisen's twitter: http://twitter.com/phyloge... - Steve Koch from Bookmarklet

Try: http://twitter.com/phyloge... - Jim Till

Thanks, corrected - Steve Koch

Fun to watch someone so passionate and happy about his life work. From Daniel Lemire on friendfeed: http://friendfeed.com/lemire... - Steve Koch

Is now a good time to mention the myth about how D2O can cause neurological disorders. Its very popular amongst the neutron scattering community because we swim in the stuff. - Cameron Neylon

Don't even get me started on the deuterium dreams I've been having lately :) - Steve Koch

"Deuterium oxide (heavy water; D(2)O) has previously been reported to have a protective effect on biomolecules (proteins and nucleic acids), cells and simple multicellular organisms against thermal shock." - Steve Koch

Also, I gave a little update at group meeting today that has some links at the end: http://www.slideshare.net/skoch3... - Steve Koch

comment={} Chemico-biological interactions, Vol. 117, No. 3. (12 February 1999), pp. 191-217. The topic of deuterium isotope effects is usually concerned with the effects on chemical reactions that are caused by the substitution of deuterium atoms for protium, or hydrogen, atoms in a molecule. These effects include changes in the rate of cleavage of covalent bonds to deuterium, or to an atom located adjacent to deuterium, in a reactant molecule. Deuterium isotope effects on other, noncovalent, interactions between molecules are known to occur, but they are generally considered to be insignificant, especially in biological experiments where deuterium substituted molecules are used as tracers. Noncovalent interactions between molecules include hydrogen bonding, and ionic and van der Waals interactions. This article reviews evidence for deuterium isotope effects on noncovalent interactions, with an emphasis on binding interactions between molecules of biological interest, but also... - Steve Koch

I only read a few parts of this review, but I think it has some valuable parts, especially since Wade is trying to focus on reviewing isotope affects that are unlikely due to direct involvement of a deuterium bond in a chemical reaction. For example, effects on biomolecular interactions due to the differences in the solvent. There is a very interesting section which reviews some prior... more... - Steve Koch

Cited by the 2008 Fernandez single-molecule D2O paper. Sheu SY, Schlag EW, Selzle HL, Yang DY. "... Furthermore, water produces a very large change in the entropy of activation due to the hydrogen bond breakage, which affects the rate by as much as 2 orders of magnitude. We also observe that there is an entire ensemble of H-bond structures, rather than a single transition state, all of which contribute to this H-bond. Here the model is tested by changing to D2O as the surrounding medium resulting in a substantial solvent isotope effect. This demonstrates the important influence of the environment on the individual hydrogen bond." - Steve Koch

Phys Rev Lett. 2008 Aug 8;101(6):065502. Epub 2008 Aug 6. Soper AK, Benmore CJ. The structures of heavy and light water at ambient conditions are investigated with the combined techniques of x-ray diffraction, neutron diffraction, and computer simulation. It is found that heavy water is a more structured liquid than light water. We find the OH bond length in H2O is approximately 3% longer than the OD bond length in D2O. This is a much larger change than current predictions. Corresponding to this, the hydrogen bond in light water is approximately 4% shorter than in heavy water, while the intermolecular HH distance is approximately 2% longer. PMID: 18764471 - Steve Koch

This is another version of mfold specifically designed for hybridizing oligos. I like it. - Steve Koch

Dang, Looks like we were beat to the punch for some of our ideas! But at least it's not kinesin motility and it also shows that we're thinking of good experiments, because this is one of the best single-molecule groups out there. I don't have access to the paper but have requested it on ILL. "We present an array of force spectroscopy experiments that aim to identify the role of solvent hydrogen bonds in protein folding and chemical reactions at the single-molecule level. In our experiments we control the strength of hydrogen bonds in the solvent environment by substituting water (H(2)O) with deuterium oxide (D(2)O). Using a combination of force protocols, we demonstrate that protein unfolding, protein collapse, protein folding and a chemical reaction are affected in different ways by substituting H(2)O with D(2)O. We find that D(2)O molecules form an integral part of the unfolding transition structure of the immunoglobulin module of human cardiac titin, I27. .." - Steve Koch

Got the PDF. I may put some quotes from it here. "In solution, hydrogen bonds are not rigid, but rather fluxional on a time scale of 50 ps.[12]" [12] 5.1. Sheu, E. W. Schlag, H. L. Selzle, D.Y. Yang, J. Phys. Chem. A 2008, 772, 797-802. I'd like to look at that paper. - Steve Koch

Panda D, Chakrabarti G, Hudson J, Pigg K, Miller HP, Wilson L, Himes RH. The authors study the D2O suppression of many aspects of microtubule instability. For example, 89% D2O reduces the steady-state GTPase activity by 90% - Steve Koch

Liang J, Fernández JM. "Single-molecule force-clamp spectroscopy offers a novel platform for mechanically denaturing proteins by applying a constant force to a polyprotein. A powerful emerging application of the technique is that, by introducing a disulfide bond in each protein module, the chemical kinetics of disulfide bond cleavage under different stretching forces can be probed at the single-bond level. Even at forces much lower than that which can rupture the chemical bond, the breaking of the S-S bond at the presence of various chemical reducing agents is significantly accelerated. Our previous work demonstrated that the rate of thiol/disulfide exchange reaction is force-dependent and well-described by an Arrhenius term of the form r = A(exp((FDeltax(r) - E(a))/k(B)T)[nucleophile]). From Arrhenius fits to the force dependency of the reduction rate, we measured the bond elongation parameter, ... PMID: 19572737 - Steve Koch

Bradley group experiment to see if a small set of people can distinguish between deuterated and non-deuterated solvents based on smell. - Steve Koch

Linked by Bradley on this thread: http://friendfeed.com/steveko... - Steve Koch

The role of naturally occurring D in living organisms has been examined by using deuterium-depleted water (30-40 ppm D) instead of water containing the natural abundance of D (150 ppm). The deuterium-depleted water significantly decreased the growth rate of the L929 fibroblast cell line, and also inhibited the tumor growth in xenotransplanted mice. Eighty days after transplantation in 10 (59%) out of 17 tumorous mice the tumor, after having grown, regressed and then disappeared. We suggest that the naturally occurring D has a central role in signal transduction involved in cell cycle regulation. - Steve Koch

Hey Jean-Claude, Interesting smell reference in a review I'm reading: "2.5.1. Olfaction in fish. Hara [40] investigated the ability of the whitefish, Coregonus clupeaformis, to distinguish between the odor of glycine (Gly) and fully deuterated glycine (Gly-ds). Over the concentration range of 10^-8 to 10^-4 M, these fish avoided solutions of Gly-ds and preferred solutions of Gly." From:... more... - Steve Koch

Tubulin is an unstable protein when stored in solution and loses its ability to form microtubules rapidly. We have found that D2O stabilizes the protein against inactivation at both 4 and 37 degrees C....We suggest that the combination of D2O and DMSO, both stimulators of tubulin assembly, leads to the rapid production of nuclei that lead to the formation of ribbon structures rather than microtubules. - Steve Koch

Are you saying for the people who originally studied it? Or for our group? Or just lamenting the way science is funded? - Steve Koch

comment={} Biochemistry, Vol. 38, No. 10. (9 March 1999), pp. 3067-3072. Tubulin is an unstable protein when stored in solution and loses its ability to form microtubules rapidly. We have found that D2O stabilizes the protein against inactivation at both 4 and 37 degrees C. In H2O-based buffer, tubulin was completely inactivated after 40 h at 4 degrees C, but in buffer prepared in D2O, no activity was lost after 54 h. Tubulin was completely inactivated at 37 degrees C in 8 h in H2O buffer, but only 20% of the activity was lost in D2O buffer. Tubulin also lost its colchicine binding activity at a slower rate in D2O. The deuterated solvent retarded an aggregation process that occurs during incubation at both temperatures. Inactivation in H2O buffer was partially reversed by transferring the protein to D2O buffer; however, aggregation was not reversed. The level of binding of BisANS, a probe of exposed hydrophobic sites in proteins, increases during the inactivation of tubulin. In D2O,... - Steve Koch

"...In addition, D2O strongly suppressed the GTP hydrolysis rate of microtubules, but it had no effect on the initial rate of GTP hydrolysis of the FtsZ assembly. D2O (80%) also increased the helical content of FtsZ by 25% compared to the helical content of FtsZ in aqueous buffer. D2O was shown to reduce the binding of 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid (bis-ANS) to tubulin. In contrast, we found that D2O strongly enhanced the binding of bis-ANS to FtsZ. The results indicated that D2O promotes assembly and bundling of FtsZ protofilaments by increasing hydrophobic interactions between the protofilaments. The results also suggest that the phosphate release rather than the on-site GTP hydrolysis is the rate-limiting step of the GTP turnover reaction." - Steve Koch

2005 Review by Cleland - Steve Koch

"The present study was aimed to elucidate the mechanism of stabilization of tubulin by deuterium oxide (D(2)O). Rate of decrease of tryptophan fluorescence during aging of tubulin at 4 degrees C and 37 degrees C was significantly lower in D(2)O than in H(2)O. Circular dichroism spectra of tubulin after incubation at 4 degrees C, suggested that complete stabilization of the secondary structure in D(2)O during the first 24 hours of incubation. The number of available cysteine measured by DTNB reaction was decreased to a lesser extent in D(2)O than in H(2)O. During the increase in temperature of tubulin, the rate of decrease of fluorescence at 335 nm and change of CD value at 222 nm was lesser in D(2)O. Differential Scanning calorimetric experiments showed that the T(m) values for tubulin unfolding in D(2)O were 58.6 degrees C and 62.17 degrees C, and in H(2)O those values were 55.4 degrees C and 59.35 degrees C." - Steve Koch

"The topic of deuterium isotope effects is usually concerned with the effects on chemical reactions that are caused by the substitution of deuterium atoms for protium, or hydrogen, atoms in a molecule. These effects include changes in the rate of cleavage of covalent bonds to deuterium, or to an atom located adjacent to deuterium, in a reactant molecule. Deuterium isotope effects on other, noncovalent, interactions between molecules are known to occur, but they are generally considered to be insignificant, especially in biological experiments where deuterium substituted molecules are used as tracers. Noncovalent interactions between molecules include hydrogen bonding, and ionic and van der Waals interactions. This article reviews evidence for deuterium isotope effects on noncovalent interactions, with an emphasis on binding interactions between molecules of biological interest, but also including examples of nonbiological molecules in order to demonstrate the generality of these eff... - Steve Koch

"The introduction of deuterium in place of protium in the hydrogenic sites of water, and its consequent exchange into some positions of enzymes and substrates, produces solvent isotope effects on the kinetic and equilibrium constants associated with the enzymic reaction. These effects, usually expressed as ratios of the appropriate constants in the two isotopic solvents HOH and DOD, are useful in the study of reaction mechanism...The purposes ofthe present article are: (a) to give the physicochemical background for the use of solvent isotope effects in biochemical studies, with fairly complete derivations of the requisite algebraic expressions, an account of underlying assumptions, and a review of pertinent experimental and theoretical information; (b) to outline workable procedures for carrying out experiments in this area; and (c) to present the apparatus for interpretation of the results." - Steve Koch

Wow. There's a ton of information here. I have this PDF now from ILL. I am surprised, though, that keyword search for "viscosity" "diffusion" "diffusivity" doesn't get any hits. It's all about D2O exchanging with protium on molecules and changes to transitions states. - Steve Koch

Cover of Paul Simon's train in the distance - Steve Koch

"Everybody loves the sound of a grant in the distance...everybody thinks it's true." - Steve Koch

Yes: I have a proposal due tomorrow morning. "There's no way this proposal will write itself with only 12 hours remaining!" - Steve Koch

The exchange of deuterium for hydrogen in water often produces solvent kinetic isotope effects (KSIEs) on the rate constants associated with enzyme reactions, including those catalyzed by RNA. - Steve Koch

hello, world - Steve Koch from Bookmarklet

"Output: primes above 25,000,000,000: Timeout" lol - Ruchira S. Datta