Computer exploration

I received my Ph.D. in theoretical physics from the Institute of Theoretical Physics (ITP) at the State University of Stony Brook in 1988. My thesis research, entitled Computer Explorations of Discrete Complex Systems, was conducted under Professor Max Dresden, who was at the time nearing the end of his professional career a career that began when Max was studying for his own Ph.D. under Uhlen-beck (of spin fame). I was, in fact. Max s last Ph.D. student, and it was Max who one day suggested to me during one of our frequent lunches that he and I ought to write a book on cellular automata together. 

A Computational Exploration of the Modified-Chalk-Harrod Mechanism... 

COMT is, for many of the same reasons as with chorismate mutase, well suited for the study with computational techniques. The reaction mechanism it catalyzes is the same mechanism that operates in the absence of the enzyme, specifically, the S 2 mechanism, facilitating comparison of the bare solution-phase reaction with the catalyzed reaction. The subsfiate and cofactor do not covalendy bind to the enzyme, so that defining the QM region and the MM region should be relatively uncomplicated. Lasdy, the X-ray crystal structure of COMT bound with the inhibitor 3,5-dinitrocatechol has been determined with a resolution of 2 kP An interesting twist to this enzyme is that the active site includes a metal cation, Mg " ". This crystal structure allows for a natural starting point for computational exploration of the means of the catalytic action of COMT. The rate acceleration provided by COMT is substantial the reaction is 10 times faster within the enzyme than in solution. " ... 

Technically it is the existence of transcendental numbers in the number continuum that makes chaos possible. We should note, however, that this does not prevent meaningful computer exploration of chaos despite the fact that computers only deal in rational approximations to algebraic and transcendental numbers (see, e.g., Hammel et al. (1987)). This fact is illustrated in Section 2.2, where we discuss some important examples of chaotic mappings. 

A computational exploration of cation locations in high- silica Ca-Chabazite... 

Nendel, M., Sperling, D., Wiest, O., Houk, K. N. Computational Explorations of Vinylcyclopropane-Cyclopentene Rearrangements and Competing Diradical Stereoisomerizations. J. Org. Chem. 2000, 65, 3259-3268. 

First, one can experimentally measure as many fluxes (or more) as the dimension of the null-space, so as to uniquely calculate the remaining fluxesJ " This approach is called metabolic flux analysis. Alternatively, an objective of the metabolic network can be chosen to computationally explore the best use of the metabolic network by a given metabolic genotype. Herein, we pursue the second option. The solution to Eq. (7) subject to the linear inequality constraints can be formulated as a linear programming (LP) problem, in which one finds fhe flux distribution that minimizes a particular objective. Mathematically, the LP problem is stated as ... 

Flux balance analysis has been used for over 15 yr to study the metabolic flux distribution. Initially, the applications of FBA were primarily educational however, recently, the utility has grown. The FBA has been applied to study the effect of gene deletions, the design of bacterial metabolism for industrial and environmental applications, or for the computational exploration of cellular physiology. Metabolic engineering has been successfully applied to engineer micro-organisms to produce valuable biochemicals... 

Computer explorations) For each of the following reversible systems, try to sketch the phase portrait by hand. Then use a computer to check your sketch. If the computer reveals patterns you hadn t anticipated, try to explain them. 

Second-order phase-locked loop) Using a computer, explore the phase portrait of 0 + (l- cos0)0 + sin0 = O for //>0. For some values of fi, you should find that the system has a stable limit cycle. Classify the bifurcations that create and destroy the cycle as jz increases from 0. 

Langley, P., Simon, H., Bradshaw, G., Zytkow. J. 1987. Scientific Discovery Computational Explorations of the Creative Processes. Cambridge, MA MIT Press. 

Computational chemistry is fairly cheap, it is fast compared to experiment, and it is environmentally safe. It does not replace experiment, which remains the final arbiter of truth about Nature. Furthermore, to make something - new drugs, new materials - one has to go into the lab. However, computation has become so reliable in some respects that, more and more, scientists in general are employing it before embarking on an experimental project, and the day may come when to obtain a grant for some kinds of experimental work you will have to show to what extent you have computationally explored the feasibility of the proposal. 

FIGURE 14.2 Novel pathways for 3-HP biosynthesis designed by Biochemical Network Integrated Computational Explorer (BNICE) (Henry et al., 2010). 

BNICE Biochemical Network Integrated Computational Explorer... 

M. Caudill and C. Butlei Understanding Neural Networks Computer Explorations, Bradford Books/MIT Press, Cambridge, MA, 1992, Vols. 1 and 2. 

Three further computational explorations of carbene reaction mechanisms have been reported. DFT study of the Reimer-Tiemann reaction (formal reaction between CCl2 and a phenoxide ion) using either potassium or sodium hydroxide as base has revealed that the active carbenic species is an alkaline carbenoid form rather than its free form as suggested earlier. DFT study of the reaction of CHF with dioxygen has confirmed fhaf fhe firsf step involves formation of the planar HFCO2 adduct. The initial steps of 2,5-dimethylfuran thermal decomposition have been computationally identified as scission of the C—H bond in the methyl side chain and subsequent formation of ft- and a-carbenes (39) and (40) via [3,2]-H and [2,3]-methyl shifts, respectively (Scheme 6). Once generated, carbenes (39) and (40) are believed to follow diverse fragmentation pathways. ... 

NHC-catalysed umpolung of enals appears to be a useful tool for annulation reactions that generally induces molecular complexity from simple starting materials. Enals have thus been reported as appropriate reaction partners for asymmetric annulation reactions with isatins and benzodi(enone)s to yield spirocyclic oxindolo-y-butyrolactones (121), and polycyclic compounds (122), respectively. Both annulation processes have been catalysed by chiral NHCs and accomplished in good yields with high regio- and/or stereo-selectivities. In parallel, the mechanism of the NHC-catalysed annulation reaction of butenal with pentenone has been computationally explored at the B3LYP/6-31+G and M06-2X/6-31G levels of theory. This study has clearly emphasized the key role played by proton-transfer steps in both the rate and the course of the reaction. 

Bao X, von Deak D, Biddinger EJ, Ozkan US, Haddad CM (2010) A computational exploration of the oxygen reduction reaction over a carbon catalyst containing a phosphinate fimctiraial group. Chem Commun 46 8621-8623... 

The reaction of bromoform with cyclohexanone has been computationally explored, with a focus on the formation of dibromoepoxide (21) as key intermediate. Two mechanistic routes, involving the addition of either singlet dibromocarbene (route a) or tri-bromomethyl carbanion (route b) on the carbonyl group of cyclohexanone, have been envisaged and calculated using ab initio HF/6-311-I-I-G and MP2/6-31H-G levels of theory. While both routes have been found suitable from a thermodynamic viewpoint, the so-obtained calculations have nevertheless revealed that route b is privileged when performing the reaction in a polar protic solvent under alkaline conditions. 

The transition metal-catalysed amination of C-H bonds via reactive metal-imide intermediates (i.e., nitrenoids) remains a powerful taetie for C-N bond formation. In that context, the intramolecular C(ip )-H amination of biaryl azides as nitrenoid sources has been computationally explored regarding the nature of the transition metal that plays the catalytic role. Four common transition metals (Ir, Rh, Ru and Zn) have thus been considered, and while the calculations have revealed similar energy profiles regardless of the nature of the metal, catalytically active Ru speeies have nevertheless been shown to be the more efficient from a kinetic viewpoint. 

Snoek LC, Kroemer RT, Simons JP (2002) A spectroscopic and computational exploration of tryptophan-water cluster structures in the gas phase. Phys Chem Chem Phys 4 2130... 

The computational exploration of the conformatimial landscapes of neutral hydrated monosaccharides is particularly challenging because the relative energies of the many possible conformational structures are very close and, in some cases, the associated vibrational spectra differ only very slightly. Singly hydrated pXyl-O-Ph is a typical example of these difficulties [50]. To improve the theoretical description of such systems, more sophisticated approaches than the standard DFT calculation have been applied. Vibrational anharmonicity has been accommodated ab initio, using Vibrational Self Consistent Field (VSCF) theory, and has reproduced very accurately the observed spectra [47, 50, 53]. The conformational interconversion of hydrated monosaccharides has been simulated using Ab Initio... 

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