***TASK***
the task is to simplify the input abstract of a biomedical literature

***INPUT***
the input is the abstract of a biomedical literature

***OUTPUT***
the output is the simplified abstract for the input abstract of a biomedical literature
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Input: Functionally analogous enzymes are those that catalyze similar reactions on similar substrates but do not share common ancestry, providing a window on the different structural strategies nature has used to evolve required catalysts. Identification and use of this information to improve reaction classification and computational annotation of enzymes newly discovered in the genome projects would benefit from systematic determination of reaction similarities. Here, we quantified similarity in bond changes for overall reactions and catalytic mechanisms for 95 pairs of functionally analogous enzymes (non-homologous enzymes with identical first three numbers of their EC codes) from the MACiE database. Similarity of overall reactions was computed by comparing the sets of bond changes in the transformations from substrates to products. For similarity of mechanisms, sets of bond changes occurring in each mechanistic step were compared; these similarities were then used to guide global and local alignments of mechanistic steps. Using this metric, only 44% of pairs of functionally analogous enzymes in the dataset had significantly similar overall reactions. For these enzymes, convergence to the same mechanism occurred in 33% of cases, with most pairs having at least one identical mechanistic step. Using our metric, overall reaction similarity serves as an upper bound for mechanistic similarity in functional analogs. For example, the four carbon-oxygen lyases acting on phosphates (EC 4.2.3) show neither significant overall reaction similarity nor significant mechanistic similarity. By contrast, the three carboxylic-ester hydrolases (EC 3.1.1) catalyze overall reactions with identical bond changes and have converged to almost identical mechanisms. The large proportion of enzyme pairs that do not show significant overall reaction similarity (56%) suggests that at least for the functionally analogous enzymes studied here, more stringent criteria could be used to refine definitions of EC sub-subclasses for improved discrimination in their classification of enzyme reactions. The results also indicate that mechanistic convergence of reaction steps is widespread, suggesting that quantitative measurement of mechanistic similarity can inform approaches for functional annotation.
Output:  When species evolve, their genes duplicate and diverge to allow for adaptation of their functional repertoires to the changing environment. In this scenario, unrelated genes can convergently evolve to produce proteins with the same molecular function, termed “functionally analogous.” A quantitative determination of the reaction similarities among functionally analogous enzymes could provide insight about the different structural solutions nature has used to evolve similar catalysts. Bond changes between substrates and products, and between successive reaction intermediates, were used to compare the reactions catalyzed and the mechanisms of catalysis for 95 pairs of functionally analogous enzymes. Less than half of the reactions catalyzed by unrelated enzymes, but defined as similar by the Enzyme Commission (EC) classification, are similar in terms of bond changes, suggesting that this classification often fails to capture quantitative differences between many enzyme reactions. Furthermore, we addressed for the first time whether the chemical mechanisms by which similar overall reactions are achieved in functional analogs are also similar. We conclude that convergence of reaction is often accompanied by convergence of chemical mechanism. These results will be useful for classifying enzymes, guiding functional annotation of newly determined enzyme sequences and structures and for informing the engineering of enzymes with new functions.

Input:  Cells of the embryonic vertebrate limb in high-density culture undergo chondrogenic pattern formation, which results in the production of regularly spaced “islands” of cartilage similar to the cartilage primordia of the developing limb skeleton. The first step in this process, in vitro and in vivo, is the generation of “cell condensations,” in which the precartilage cells become more tightly packed at the sites at which cartilage will form. In this paper we describe a discrete, stochastic model for the behavior of limb bud precartilage mesenchymal cells in vitro. The model uses a biologically motivated reaction–diffusion process and cell-matrix adhesion (haptotaxis) as the bases of chondrogenic pattern formation, whereby the biochemically distinct condensing cells, as well as the size, number, and arrangement of the multicellular condensations, are generated in a self-organizing fashion. Improving on an earlier lattice-gas representation of the same process, it is multiscale (i.e., cell and molecular dynamics occur on distinct scales), and the cells are represented as spatially extended objects that can change their shape. The authors calibrate the model using experimental data and study sensitivity to changes in key parameters. The simulations have disclosed two distinct dynamic regimes for pattern self-organization involving transient or stationary inductive patterns of morphogens. The authors discuss these modes of pattern formation in relation to available experimental evidence for the in vitro system, as well as their implications for understanding limb skeletal patterning during embryonic development.


Output:

The development of an organism from embryo to adult includes processes of pattern formation that involve the interactions over space and time of independent cells to form multicellular structures. Computational models permit exploration of possible alternative mechanisms that reproduce biological patterns and thereby provide hypotheses for empirical testing. In this article, we describe a biologically motivated discrete stochastic model that shows that the patterns of spots and stripes of tightly packed cells observed in cultures derived from the embryonic vertebrate limb can occur by a mechanism that uses only cell–cell signaling via diffusible molecules (morphogens) and cell substratum adhesion (haptotaxis). Moreover, similar-looking patterns can arise both from stable stationary dynamics and unstable transient dynamics of the same underlying core molecular–genetic mechanism. Simulations also show that spot and stripe patterns (which also correspond to the nodules and bars of the developing limb skeleton in vivo) are close in parameter space and can be generated in multiple ways with single-parameter variations. An important implication is that some developmental processes do not require a strict progression from one stable dynamic regime to another, but can occur by a succession of transient dynamic regimes tuned (e.g., by natural selection) to achieve a particular morphological outcome.
