Understanding the enzymatic activity of 4-oxalocrotonate tautomerase and its mutant analogues: a computational study

The effect of replacing arginine residues (Arg) with citrulline residues (Cit) in the binding site of 4-oxalocrotonate tautomerase (4-OT) was investigated with force field molecular dynamics and hybrid quantum mechanics/molecular mechanics studies. It is found that the Arg61Cit mutation has only minor effects on the k(cat) and K(M) values determined experimentally because of the flexibility of this residue. The decrease in k(cat) and increase in K(M) for the Arg11Cit and Arg39Cit mutations are due to the disruption of the binding site, which arises from repulsive interactions with neighboring residues. The results of this investigation shed new light on the effects of mutations in the binding site of 4-OT and consequently on how the enzyme binds the active substrate.     

Sharp thresholds of graph properties, and the -sat problem

Given a monotone graph property , consider , the probability that a random graph with edge probability will have . The function is the key to understanding the threshold behavior of the property . We show that if is small (corresponding to a non-sharp threshold), then there is a list of graphs of bounded size such that can be approximated by the property of having one of the graphs as a subgraph. One striking consequence of this result is that a coarse threshold for a random graph property can only happen when the value of the critical edge probability is a rational power of .

As an application of the main theorem we settle the question of the existence of a sharp threshold for the satisfiability of a random -CNF formula.

An appendix by Jean Bourgain was added after the first version of this paper was written. In this appendix some of the conjectures raised in this paper are proven, along with more general results.

     

Femtosecond pump-probe measurements of solvation by hydrogen-bonding interactions.

An additional ultrafast blue shift in the transient absorption spectra of hydrogen-bonding complexes of a strong photoacid, 8-hydroxypyrene 1,3,6-trisdimethylsulfonamide (HPTA), over the solvation response of the uncomplexed HPTA and also over that of the methoxy derivative of the photoacid (MPTA) in the presence of the hydrogen-bonding base was observed on optical excitation of the photoacid. The additional 55 +/- 10 fs solvation response was found to be about 35 % and 19% of the total C(t) of HPTA in dichloromethane (DCM) when it was hydrogen-bonded to dimethylsulfoxide (DMSO) and dioxane, respectively, and about 29% of the total C(t) of HPTA in dichloroethane (DCE) when it was hydrogen-bonded to DMSO. We have assigned this additional dynamic spectral shift to a transient change in the hydrogen bond (O-H...O) that links HPTA to the complexing base, after the electronic excitation of the photoacid.     

Chlorine Dioxide as an Electron-Transfer Oxidant of Olefins. Preliminary Communication

The kinetics and product studies of oxidation of eight olefins 1 - 8 by ClO₂ in H₂O in the pH range 3-7 are described. The reaction is faster as the pH decreases. At pH < 4, ClO₂ reacts equimolarly with olefins to yield isomeric mixtures of chlorohydrines and 1,2-dioxygenated products, following the equation: The order of reactivity is: (E)-stilbene > indene > β-methylstyrene > acenaphthylene > α-methylstyrene > styrene > cyclohexene > allylbenzene. A multi-stage radical-cation mechanism is proposed, in which an initial reversible protonation: is followed by an electron-transfer stage (rate-determining): The cation-radical thus produced, adds rapidly an additional ClO₂ to form dioxygenated products. The chlorohydrines most likely arise from HClO additions to the olefinic double bonds, which, in turn, generate from dismutation of 2 HClO₂ into HClO + H⁺ + ClO.     

Antibody-catalyzed benzoin oxidation as a mechanistic probe for nucleophilic catalysis by an active site lysine

Aldolase antibody 24H6, which was obtained by reactive immunization against a 1,3-diketone hapten, is shown to catalyze additional reactions, including H/D exchange and oxidation reactions. Comparison of the H/D exchange reaction at the alpha-position of a wide range of aldehydes and ketones by 24H6 and by other aldolase antibodies, such as 38C2, pointed at the significantly larger size of the 24H6 active site. This property allowed for the catalysis of the oxidation of substituted benzoins to benzils by potassium ferricyanide. This reaction was used as a mechanistic probe to learn about the initial steps of the 24H6-catalyzed aldol condensation reaction. The Hammett correlation (rho=4.7) of log(k(cat)) versus the substituent constant, sigma, revealed that the reaction involves rapid formation of a Schiff base intermediate from the ketone and an active site lysine residue. The rate-limiting step in this oxidation reaction is the conversion of the Schiff base to an enamine intermediate. In addition, linear correlation (rho=3.13) was found between log(K(M)) and sigma, indicating that electronic rather than steric factors are dominant in the antibody-substrate binding phenomenon and confirming that the reversible formation of a Schiff base intermediate comprises part of the substrate-binding mechanism.     

Oscillating superfluidity of bosons in optical lattices

Following a suggestion by Orzel et al. [Science 291, 2386 (2001)]], we analyze bosons in an optical lattice undergoing a sudden parameter change from the Mott to superfluid phase. We introduce a modified coherent states path integral to describe both phases. The saddle point theory yields collective oscillations of the uniform superfluid order parameter. We calculate its damping rate by phason pair emission. In two dimensions the overdamped region largely overlaps with the quantum critical region. Measurements of critical dynamics on the Mott side are proposed.     

Self-segregation versus clustering in the evolutionary minority game

Complex adaptive systems have been the subject of much recent attention. It is by now well established that members ("agents") tend to self-segregate into opposing groups characterized by extreme behavior. However, the study of such adaptive systems has mostly been restricted to simple situations in which the prize-to-fine ratio R equals unity. In this Letter we explore the dynamics of evolving populations with various different values of the ratio R, and demonstrate that extreme behavior is in fact not a generic feature of adaptive systems. In particular, we show that "confusion" and "indecisiveness" take over in times of depression, in which case cautious agents perform better than extreme ones.