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10.1016/j.chembiol.2021.05.018 http://scihub22266oqcxt.onion/10.1016/j.chembiol.2021.05.018 34174194!8228784!34174194     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Cell+Chem+Biol 2021 ; 28 (12): 1795-1806.e5 Nephropedia Template TP {{tp|p=34174194|t=2021. An automatic pipeline for the design of irreversible derivatives identifies a potent SARS-CoV-2 M(pro) inhibitor |pdf=|usr=}}{{34174194}} gab.com Text An automatic pipeline for the design of irreversible derivatives identifies a potent SARS-CoV-2 M(pro) inhibitor JO: Cell Chem Biol http://www.kidney.de/pget.php?&tw=1&pmid=34174194 #FOAvip Designing covalent inhibitors is increasingly important, although it remains challenging. Here, we present covalentizer, a computational pipeline for identifying irreversible inhibitors based on structures of targets with non-covalent binders. Through covalent docking of tailored focused libraries, we identify candidates that can bind covalently to a nearby cysteine while preserving the interactions of the original molecule. We found approximately 11,000 cysteines proximal to a ligand across 8,386 complexes in the PDB. Of these, the protocol identified 1,553 structures with covalent predictions. In a prospective evaluation, five out of nine predicted covalent kinase inhibitors showed half-maximal inhibitory concentration (IC(50)) values between 155 nM and 4.5 muM. Application against an existing SARS-CoV M(pro) reversible inhibitor led to an acrylamide inhibitor series with low micromolar IC(50) values against SARS-CoV-2 M(pro). The docking was validated by 12 co-crystal structures. Together these examples hint at the vast number of covalent inhibitors accessible through our protocol. Twit Text FOAVip An automatic pipeline for the design of irreversible derivatives identifies a potent SARS-CoV-2 M(pro) inhibitor ????Cell Chem Biol http://www.kidney.de/pget.php?&tw=1&pmid=34174194 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34174194 #FOAvip English Wikipedia <ref>{{Cite pmid|34174194}}</ref> An automatic pipeline for the design of irreversible derivatives identifies a potent SARS-CoV-2 M(pro) inhibitor #MMPMID34174194 Zaidman D; Gehrtz P; Filep M; Fearon D; Gabizon R; Douangamath A; Prilusky J; Duberstein S; Cohen G; Owen CD; Resnick E; Strain-Damerell C; Lukacik P; Barr H; Walsh MA; von Delft F; London N Cell Chem Biol 2021[Dec]; 28 (12): 1795-1806.e5 PMID34174194show ga Designing covalent inhibitors is increasingly important, although it remains challenging. Here, we present covalentizer, a computational pipeline for identifying irreversible inhibitors based on structures of targets with non-covalent binders. Through covalent docking of tailored focused libraries, we identify candidates that can bind covalently to a nearby cysteine while preserving the interactions of the original molecule. We found approximately 11,000 cysteines proximal to a ligand across 8,386 complexes in the PDB. Of these, the protocol identified 1,553 structures with covalent predictions. In a prospective evaluation, five out of nine predicted covalent kinase inhibitors showed half-maximal inhibitory concentration (IC(50)) values between 155 nM and 4.5 muM. Application against an existing SARS-CoV M(pro) reversible inhibitor led to an acrylamide inhibitor series with low micromolar IC(50) values against SARS-CoV-2 M(pro). The docking was validated by 12 co-crystal structures. Together these examples hint at the vast number of covalent inhibitors accessible through our protocol. |*Drug Design[MESH] |Acrylamide/chemistry/metabolism[MESH] |Binding Sites[MESH] |COVID-19/pathology/virology[MESH] |Catalytic Domain[MESH] |Computational Biology/methods[MESH] |Databases, Protein[MESH] |Humans[MESH] |Inhibitory Concentration 50[MESH] |Molecular Docking Simulation[MESH] |Protein Kinase Inhibitors/*chemistry/metabolism[MESH] |SARS-CoV-2/*enzymology/isolation & purification[MESH]An automatic pipeline for the design of irreversible derivatives ident(epmc).pdf DeepDyve Pubget Overpricing