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10.1007/s00894-021-04779-0 http://scihub22266oqcxt.onion/10.1007/s00894-021-04779-0 34057647!8165686!34057647     free     free     free Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Mol+Model 2021 ; 27 (6): 191 Nephropedia Template TP {{tp|p=34057647|t=2021. Plausible blockers of Spike RBD in SARS-CoV2-molecular design and underlying interaction dynamics from high-level structural descriptors |pdf=|usr=}}{{34057647}} gab.com Text Plausible blockers of Spike RBD in SARS-CoV2-molecular design and underlying interaction dynamics from high-level structural descriptors JO: J Mol Model http://www.kidney.de/pget.php?&tw=1&pmid=34057647 #FOAvip COVID-19 is characterized by an unprecedented abrupt increase in the viral transmission rate (SARS-CoV-2) relative to its pandemic evolutionary ancestor, SARS-CoV (2003). The complex molecular cascade of events related to the viral pathogenicity is triggered by the Spike protein upon interacting with the ACE2 receptor on human lung cells through its receptor binding domain (RBD(Spike)). One potential therapeutic strategy to combat COVID-19 could thus be limiting the infection by blocking this key interaction. In this current study, we adopt a protein design approach to predict and propose non-virulent structural mimics of the RBD(Spike) which can potentially serve as its competitive inhibitors in binding to ACE2. The RBD(Spike) is an independently foldable protein domain, resilient to conformational changes upon mutations and therefore an attractive target for strategic re-design. Interestingly, in spite of displaying an optimal shape fit between their interacting surfaces (attributed to a consequently high mutual affinity), the RBD(Spike)-ACE2 interaction appears to have a quasi-stable character due to a poor electrostatic match at their interface. Structural analyses of homologous protein complexes reveal that the ACE2 binding site of RBD(Spike) has an unusually high degree of solvent-exposed hydrophobic residues, attributed to key evolutionary changes, making it inherently "reaction-prone." The designed mimics aimed to block the viral entry by occupying the available binding sites on ACE2, are tested to have signatures of stable high-affinity binding with ACE2 (cross-validated by appropriate free energy estimates), overriding the native quasi-stable feature. The results show the apt of directly adapting natural examples in rational protein design, wherein, homology-based threading coupled with strategic "hydrophobic <--> polar" mutations serve as a potential breakthrough. Twit Text FOAVip Plausible blockers of Spike RBD in SARS-CoV2-molecular design and underlying interaction dynamics from high-level structural descriptors ????J Mol Model http://www.kidney.de/pget.php?&tw=1&pmid=34057647 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34057647 #FOAvip English Wikipedia <ref>{{Cite pmid|34057647}}</ref> Plausible blockers of Spike RBD in SARS-CoV2-molecular design and underlying interaction dynamics from high-level structural descriptors #MMPMID34057647 Basu S; Chakravarty D; Bhattacharyya D; Saha P; Patra HK J Mol Model 2021[May]; 27 (6): 191 PMID34057647show ga COVID-19 is characterized by an unprecedented abrupt increase in the viral transmission rate (SARS-CoV-2) relative to its pandemic evolutionary ancestor, SARS-CoV (2003). The complex molecular cascade of events related to the viral pathogenicity is triggered by the Spike protein upon interacting with the ACE2 receptor on human lung cells through its receptor binding domain (RBD(Spike)). One potential therapeutic strategy to combat COVID-19 could thus be limiting the infection by blocking this key interaction. In this current study, we adopt a protein design approach to predict and propose non-virulent structural mimics of the RBD(Spike) which can potentially serve as its competitive inhibitors in binding to ACE2. The RBD(Spike) is an independently foldable protein domain, resilient to conformational changes upon mutations and therefore an attractive target for strategic re-design. Interestingly, in spite of displaying an optimal shape fit between their interacting surfaces (attributed to a consequently high mutual affinity), the RBD(Spike)-ACE2 interaction appears to have a quasi-stable character due to a poor electrostatic match at their interface. Structural analyses of homologous protein complexes reveal that the ACE2 binding site of RBD(Spike) has an unusually high degree of solvent-exposed hydrophobic residues, attributed to key evolutionary changes, making it inherently "reaction-prone." The designed mimics aimed to block the viral entry by occupying the available binding sites on ACE2, are tested to have signatures of stable high-affinity binding with ACE2 (cross-validated by appropriate free energy estimates), overriding the native quasi-stable feature. The results show the apt of directly adapting natural examples in rational protein design, wherein, homology-based threading coupled with strategic "hydrophobic <--> polar" mutations serve as a potential breakthrough. |Angiotensin-Converting Enzyme 2/metabolism[MESH] |Binding Sites/physiology[MESH] |COVID-19/metabolism/transmission/virology[MESH] |Humans[MESH] |Lung/metabolism/virology[MESH] |Protein Binding/physiology[MESH] |SARS-CoV-2/*pathogenicity[MESH] |Spike Glycoprotein, Coronavirus/*antagonists & inhibitors[MESH]Plausible blockers of Spike RBD in SARS-CoV2-molecular design and unde(epmc).pdf DeepDyve Pubget Overpricing