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Sanyal, D.

Publications and source records attributed to Sanyal, D..

2 recordsLinked to original sources

IMMUND: an Early Stage Diagnostic and Therapeutic Frame for Neurodegenerative Diseases and Multiple Sclerosis based on Immunological Markers

For neurodegenerative diseases, the impact of immunological markers is one of the modern research areas. It has been observed that neuroinflammation increases the cellular precipitation of some of the key proteins associated with neurodegenerative diseases. Therefore, the possibility of functional loss can be enhanced due to neuroinflammation which leads to the initiation of any related diseases. In this regard, autoantibodies, which are known for their autophagy nature, can be considered as key elements for early diagnostic as well as early therapeutics. In this article, we have proposed a comprehensive framework to unveil the diagnostic as well as the therapeutic possibility of the autoantibodies which are largely associated with Mild-Moderate Alzheimers Disease, Early-Stage Parkinsons Disease, and Multiple Sclerosis. Here, we have introduced a new concept of average p-value where multiple p-values of an autoantibody in a singular disease have been considered as a multi-occurrence of that sample in cellular systems. Also, multiple proteins from a single protein family under a differentially expressed range have been prioritized. As a result, the top ten autoantibodies have been selected for further study and also considered as diagnostic markers. Interestingly, most of the selected autoantibodies are either cytokines or immunoglobulins. Subsequently, we have performed an evolutionary sequence-structure space study to identify the druggable structural facet for the selected autoantibodies. To make the therapeutic perspective more robust, we have introduced the concept of protein moonlighting. Hence, it provides more robustness in therapeutic identification. Finally, two autoantibodies i.e., Q9NYV4 and P01602 are identified as a novel marker.

neuroscience↗

An exploration of the SARS-CoV-2 spike receptor binding domain (RBD), a complex palette of evolutionary and structural features

SARS-CoV-2 spike protein (S) is associated with the entry of virus inside the host cell by recruiting its loop dominant receptor binding domain (RBD) and interacting with the host ACE2 receptor. Our study deploying a two-tier approach encompassing evolutionary and structural analysis provides a comprehensive picture of the RBD, which could be of potential use for better understanding the RBD and address its druggability issues. Resorting to an ensemble of sequence space exploratory tools including co-evolutionary analysis and deep mutational scans we provide a quantitative insight into the evolutionarily constrained subspace of the RBD sequence space. Guided by structure network analysis and Monte Carlo simulation we highlight regions inside the RBD, which are critical for providing structural integrity and conformational flexibility of the binding cleft. We further deployed fuzzy C-means clustering by plugging the evolutionary and structural features of discrete structure blocks of RBD to understand which structure blocks share maximum overlap based on their evolutionary and structural features. Deploying this multi-tier interlinked approach, which essentially distilled the evolutionary and structural features of RBD, we highlight discrete region, which could be a potential druggable pocket thereby destabilizing the structure and addressing evolutionary routes.

biophysics↗