Browsing by Subject "principal components analysis"

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    Identification of Phytoconstituents as Potent Inhibitors of Casein Kinase-1 Alpha Using Virtual Screening and Molecular Dynamics Simulations
    (2021-12-15) Shafie, Alaa; Khan, Shama; Zehra; Mohammad, Taj; Anjum, Farah; Hasan, Gulam Mustafa; Yadav, Dharmendra Kumar; Hassan, Md. Imtaiyaz
    Casein kinase-1 alpha (CK1α) is a multifunctional protein kinase that belongs to the serine/threonine kinases of the CK1α family. It is involved in various signaling pathways associated with chromosome segregation, cell metabolism, cell cycle progression, apoptosis, autophagy, etc. It has been known to involve in the progression of many diseases, including cancer, neurodegeneration, obesity, and behavioral disorders. The elevated expression of CK1α in diseased conditions facilitates its selective targeting for therapeutic management. Here, we have performed virtual screening of phytoconstituents from the IMPPAT database seeking potential inhibitors of CK1α. First, a cluster of compounds was retrieved based on physicochemical parameters following Lipinski’s rules and PAINS filter. Further, high-affinity hits against CK1α were obtained based on their binding affinity score. Furthermore, the ADMET, PAINS, and PASS evaluation was carried out to select more potent hits. Finally, following the interaction analysis, we elucidated three phytoconstituents, Semiglabrinol, Curcusone_A, and Liriodenine, posturing considerable affinity and specificity towards the CK1α binding pocket. The result was further evaluated by molecular dynamics (MD) simulations, dynamical cross-correlation matrix (DCCM), and principal components analysis (PCA), which revealed that binding of the selected compounds, especially Semiglabrinol, stabilizes CK1α and leads to fewer conformational fluctuations. The MM-PBSA analysis suggested an appreciable binding affinity of all three compounds toward CK1α.
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    North Atlantic climate variability from a self-organizing map perspective
    (2007) Reusch, David B; Alley, Richard B; Hewitson, Bruce C
    [1] North Atlantic variability in general, and the North Atlantic Oscillation (NAO) in particular, is a long-studied, very important but still not well-understood problem in climatology. The recent trend to a higher wintertime NAO index was accompanied by an additional increase in the Azores High not coupled to changes in the Icelandic Low, as shown by a self-organizing maps (SOMs) analysis of monthly mean DJF mean sea level pressure data from 1957 to 2002. SOMs are a nonlinear tool to optimally extract a user-specified number of patterns or icons from an input data set and to uniquely relate any input data field to an icon, allowing analyses of occurrence frequencies and transitions complementary to principal component analysis (PCA). SOMs analysis of ERA-40 data finds a North Atlantic monopole roughly colocated with the mean position of the Azores High, as well as the well-known NAO dipole involving the Icelandic Low and the subtropical high. Little trend is shown in December, but the Azores High increased along with the NAO in January and February over the study interval, with implications for storminess in northwestern Europe. In short, our SOM-based analyses of winter MSLP have both confirmed prior knowledge and expanded it through the relative ease of use and power with nonlinear systems of the SOM-based approach to climatological analysis.