Sequence paradox

The ultimate goal of protein engineering is to design an amino acid sequence that will fold into a protein with a predetermined structure and function. Paradoxically, this goal may be easier to achieve than its inverse, the solution of the folding problem. It seems to be simpler to start with a three-dimensional structure and find one of the numerous amino acid sequences that will fold into that structure than to start from an amino acid sequence and predict its three-dimensional structure. We will illustrate this by the design of a stable zinc finger domain that does not require stabilization by zinc. 

Methyl-2-furaldehyde gave a similar overall behaviour, but a penultimate effect was observed in its copolymerization with isopropenylbenzene whereby two molecules of the aldehyde could add together if the penultimate unit in the growing chain was from the olefin. This was borne out by the copolymers composition and spectra. The values of the reactivity ratios showed this interesting behaviour rx = 1.0 0.1, r2 = 0.0 0.1. An apparent paradox occurred the aldehyde, which could not homo-polymerize, had equal probability of homo- and copolymerization and the olefin, which homopolymerized readily, could only alternate. The structure arising from this situation was close to a regular sequence of the type ... 

Paradoxically, all these significant recent contributions to the theory of the ORR, together with most recent experimental efforts to characterize the ORR at a fuel cell cathode catalyst, have not led at aU to a consensus on either the mechanism of the ORR at Pt catalysts in acid electrolytes or even on how to properly determine this mechanism with available experimental tools. To elucidate the present mismatch of central pieces in the ORR puzzle, one can start from the identification of the slow step in the ORR sequence. With the 02-to-HOOads-to-HOads route appearing from recent DFT calculations to be the likely mechanism for the ORR at a Pt metal catalyst surface in acid electrolyte, the first electron and proton transfer to dioxygen, according to the reaction... 

Flutamide was the first drug used in prostate cancer therapy for which the withdrawal syndrome was reported. In that study, 40% of patients showed a decline in prostate specific antigen (PSA) levels after cessation of flutamide from the therapeutic protocol. The decline in PSA levels was associated with an improvement of the clinical symptoms. Based on these paradoxical observations, the concept of sequenced androgen ablation was proposed [217]. Several phase II clinical studies were performed, demonstrating safety and tolerability, however, a direct comparison in randomised phase III trials is necessary [218]. 

The flaw in Levinthal s analysis is that the search is assumed to be unbiased it presupposes that the groups on the protein rotate around their single bonds at random with no stabilization of any particular conformation until they are all in the right orientation, which then clicks into place. If there is a conformational bias in the sequence toward the correct structure, then the paradox disappears.21,22... 

The sad paradox is that, despite the primary importance of the latter problem convincingly substantiated in the scientific literature and the secondary role of the two former ones, UNCED documents have missed the primary importance of the following sequence of events socio-economic development (stimulated by growing population size) —> anthropogenic impact on the biosphere —> consequences of these impacts for the environment (climate, ozone, etc.). 

Then Y is an element of a non-standard sequence if Y e R and M e N. We say that YM converges to Y if Y - st Y for all infinite integers M. Continuity and differentiability can be similarly defined, for example ff(a) = st (f(a+h) - f(a) /h for all infinitesimals h. The Dirac delta function can be defined pointwise and new approaches to the theory of probability and stochastic differential equations are opened up. But these are applications and paradoxically I have been describing the abstraction that is the non-standard world in very concrete terms. This is no place to go back and try to present it abstractly, but it stands as an example of a recent step forward in the path of abstraction that began two and a half millenia ago (see also (23,24)). 

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