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10.1038/s41598-021-86471-0 http://scihub22266oqcxt.onion/10.1038/s41598-021-86471-0 33795718!8016996!33795718     free     free     free Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 280.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 280.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 280.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 280.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Sci+Rep 2021 ; 11 (1): 7429 Nephropedia Template TP {{tp|p=33795718|t=2021. Molecular dynamics and in silico mutagenesis on the reversible inhibitor-bound SARS-CoV-2 main protease complexes reveal the role of lateral pocket in enhancing the ligand affinity |pdf=|usr=}}{{33795718}} gab.com Text Molecular dynamics and in silico mutagenesis on the reversible inhibitor-bound SARS-CoV-2 main protease complexes reveal the role of lateral pocket in enhancing the ligand affinity JO: Sci Rep http://www.kidney.de/pget.php?&tw=1&pmid=33795718 #FOAvip The 2019 novel coronavirus pandemic caused by SARS-CoV-2 remains a serious health threat to humans and there is an urgent need to develop therapeutics against this deadly virus. Recent scientific evidences have suggested that the main protease (M(pro)) enzyme in SARS-CoV-2 can be an ideal drug target due to its crucial role in the viral replication and transcription processes. Therefore, there are ongoing research efforts to identify drug candidates against SARS-CoV-2 M(pro) that resulted in hundreds of X-ray crystal structures of ligand-bound M(pro) complexes in the Protein Data Bank (PDB) describing the interactions of different fragment chemotypes within different sites of the M(pro). In this work, we performed rigorous molecular dynamics (MD) simulation of 62 reversible ligand-M(pro) complexes in the PDB to gain mechanistic insights about their interactions at the atomic level. Using a total of over 3 micros long MD trajectories, we characterized different pockets in the apo M(pro) structure, and analyzed the dynamic interactions and binding affinity of ligands within those pockets. Our results identified the key residues that stabilize the ligands in the catalytic sites and other pockets of M(pro). Our analyses unraveled the role of a lateral pocket in the catalytic site in M(pro) that is critical for enhancing the ligand binding to the enzyme. We also highlighted the important contribution from HIS163 in the lateral pocket towards ligand binding and affinity against M(pro) through computational mutation analyses. Further, we revealed the effects of explicit water molecules and M(pro) dimerization in the ligand association with the target. Thus, comprehensive molecular-level insights gained from this work can be useful to identify or design potent small molecule inhibitors against SARS-CoV-2 M(pro). Twit Text FOAVip Molecular dynamics and in silico mutagenesis on the reversible inhibitor-bound SARS-CoV-2 main protease complexes reveal the role of lateral pocket in enhancing the ligand affinity ????Sci Rep http://www.kidney.de/pget.php?&tw=1&pmid=33795718 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33795718 #FOAvip English Wikipedia <ref>{{Cite pmid|33795718}}</ref> Molecular dynamics and in silico mutagenesis on the reversible inhibitor-bound SARS-CoV-2 main protease complexes reveal the role of lateral pocket in enhancing the ligand affinity #MMPMID33795718 Weng YL; Naik SR; Dingelstad N; Lugo MR; Kalyaanamoorthy S; Ganesan A Sci Rep 2021[Apr]; 11 (1): 7429 PMID33795718show ga The 2019 novel coronavirus pandemic caused by SARS-CoV-2 remains a serious health threat to humans and there is an urgent need to develop therapeutics against this deadly virus. Recent scientific evidences have suggested that the main protease (M(pro)) enzyme in SARS-CoV-2 can be an ideal drug target due to its crucial role in the viral replication and transcription processes. Therefore, there are ongoing research efforts to identify drug candidates against SARS-CoV-2 M(pro) that resulted in hundreds of X-ray crystal structures of ligand-bound M(pro) complexes in the Protein Data Bank (PDB) describing the interactions of different fragment chemotypes within different sites of the M(pro). In this work, we performed rigorous molecular dynamics (MD) simulation of 62 reversible ligand-M(pro) complexes in the PDB to gain mechanistic insights about their interactions at the atomic level. Using a total of over 3 micros long MD trajectories, we characterized different pockets in the apo M(pro) structure, and analyzed the dynamic interactions and binding affinity of ligands within those pockets. Our results identified the key residues that stabilize the ligands in the catalytic sites and other pockets of M(pro). Our analyses unraveled the role of a lateral pocket in the catalytic site in M(pro) that is critical for enhancing the ligand binding to the enzyme. We also highlighted the important contribution from HIS163 in the lateral pocket towards ligand binding and affinity against M(pro) through computational mutation analyses. Further, we revealed the effects of explicit water molecules and M(pro) dimerization in the ligand association with the target. Thus, comprehensive molecular-level insights gained from this work can be useful to identify or design potent small molecule inhibitors against SARS-CoV-2 M(pro). |*Molecular Dynamics Simulation[MESH] |Binding Sites[MESH] |COVID-19/pathology/virology[MESH] |Catalytic Domain[MESH] |Databases, Protein[MESH] |Humans[MESH] |Ligands[MESH] |Mutagenesis, Site-Directed[MESH] |Principal Component Analysis[MESH] |Protease Inhibitors/*chemistry/metabolism[MESH] |SARS-CoV-2/isolation & purification/*metabolism[MESH] |Thermodynamics[MESH]Molecular dynamics and in silico mutagenesis on the reversible inhibit(epmc).pdf DeepDyve Pubget Overpricing