Sandbox Reserved 1849: Difference between revisions

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These minibinders were designed to form stronger connections to the spike protein RBD than ACE2<ref name="Longxing">PMID:32907861</ref>. This section highlights some important residue connections with the RBD that give the minibinders higher affinities for the spike protein than ACE2.

ACE2 binds to the spike protein RBD using <scene name='10/1075251/Ace2_allbinding/2'>these residues</scene>. The minibinders are smaller than ACE2, but still form strong connections to the spike protein. This means the minibinders interact with the RBD residues more efficiently than ACE2 giving them a higher affinity for the spike protein <ref name="Longxing">PMID:32907861</ref>. AHB2 was designed to mimic ACE2 while making better use of the RBD residues giving it a higher affinity for the spike protein with an IC50 value of 15.5 nM<ref name="Longxing">PMID:32907861</ref> (<scene name='10/1075251/Ahb2_all/2'>AHB2 and RBD binding residues</scene>). LCB1 was designed from scratch to bind the most efficiently to the RBD residues giving it the highest affinity with the lowest IC50 value of 23.5 pM<ref name="Longxing">PMID:32907861</ref> (<scene name='10/1075251/Lcb1_binding_residues/2'>LCB1 and RBD binding residues</scene>). LCB3 was designed after LCB1 with the goal of making the minibinder even more efficient, however it ended up having a lower affinity than LCB1 with a higher IC50 value of 40.1 pM<ref name="Longxing">PMID:32907861</ref> (<scene name='10/1075251/Lcb3_all/2'>LCB3 and RBD binding residues</scene>).

ACE2 binds to the spike protein RBD using <scene name='10/1075251/Ace2_allbinding/3'>these residues</scene>. The minibinders are smaller than ACE2, but still form strong connections to the spike protein. This means the minibinders interact with the RBD residues more efficiently than ACE2 giving them a higher affinity for the spike protein <ref name="Longxing">PMID:32907861</ref>. AHB2 was designed to mimic ACE2 while making better use of the RBD residues giving it a higher affinity for the spike protein with an IC50 value of 15.5 nM<ref name="Longxing">PMID:32907861</ref> (<scene name='10/1075251/Ahb2_all/3'>AHB2 and RBD binding residues</scene>). LCB1 was designed from scratch to bind the most efficiently to the RBD residues giving it the highest affinity with the lowest IC50 value of 23.5 pM<ref name="Longxing">PMID:32907861</ref> (<scene name='10/1075251/Lcb1_binding_residues/3'>LCB1 and RBD binding residues</scene>). LCB3 was designed after LCB1 with the goal of making the minibinder even more efficient, however it ended up having a lower affinity than LCB1 with a higher IC50 value of 40.1 pM<ref name="Longxing">PMID:32907861</ref> (<scene name='10/1075251/Lcb3_all/2'>LCB3 and RBD binding residues</scene>).

The Glutamine-493 residue on the spike protein is an important residue in showing the differences in strength between ACE2 and the minibinders <ref name="Longxing">PMID:32907861</ref>. ACE2 does not make use of this residue when binding to the RBD. The nearest residues of ACE2, Gln35 and Lys31 do not form any interaction on Gln493 of the spike protein. The AHB2 minibinder, instead forms a Hydrogen bond on the Gln493 residue of the spike protein with its Glu41, increasing affinity to the spike protein. LCB1 forms two hydrogen bonds on Gln493 of the spike protein using two different residues, giving it the highest affinity based on the Gln493 residue. However, these interactions are not required. LCB1 forms no interactions with the Gln493 residue of the RDB previously mentioned, yet it still has a higher affinity to the RBD than AHB2 which forms a hydrogen bond with the Gln493 residue.

Sandbox Reserved 1849: Difference between revisions

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 These minibinders were designed to form stronger connections to the spike protein RBD than ACE2<ref name="Longxing">PMID:32907861</ref>. This section highlights some important residue connections with the RBD that give the minibinders higher affinities for the spike protein than ACE2.
-ACE2 binds to the spike protein RBD using <scene name='10/1075251/Ace2_allbinding/2'>these residues</scene>. The minibinders are smaller than ACE2, but still form strong connections to the spike protein. This means the minibinders interact with the RBD residues more efficiently than ACE2 giving them a higher affinity for the spike protein <ref name="Longxing">PMID:32907861</ref>. AHB2 was designed to mimic ACE2 while making better use of the RBD residues giving it a higher affinity for the spike protein with an IC<sub>50</sub> value of 15.5 nM<ref name="Longxing">PMID:32907861</ref> (<scene name='10/1075251/Ahb2_all/2'>AHB2 and RBD binding residues</scene>). LCB1 was designed from scratch to bind the most efficiently to the RBD residues giving it the highest affinity with the lowest IC<sub>50</sub> value of 23.5 pM<ref name="Longxing">PMID:32907861</ref> (<scene name='10/1075251/Lcb1_binding_residues/2'>LCB1 and RBD binding residues</scene>). LCB3 was designed after LCB1 with the goal of making the minibinder even more efficient, however it ended up having a lower affinity than LCB1 with a higher IC<sub>50</sub> value of 40.1 pM<ref name="Longxing">PMID:32907861</ref> (<scene name='10/1075251/Lcb3_all/2'>LCB3 and RBD binding residues</scene>).
+ACE2 binds to the spike protein RBD using <scene name='10/1075251/Ace2_allbinding/3'>these residues</scene>. The minibinders are smaller than ACE2, but still form strong connections to the spike protein. This means the minibinders interact with the RBD residues more efficiently than ACE2 giving them a higher affinity for the spike protein <ref name="Longxing">PMID:32907861</ref>. AHB2 was designed to mimic ACE2 while making better use of the RBD residues giving it a higher affinity for the spike protein with an IC<sub>50</sub> value of 15.5 nM<ref name="Longxing">PMID:32907861</ref> (<scene name='10/1075251/Ahb2_all/3'>AHB2 and RBD binding residues</scene>). LCB1 was designed from scratch to bind the most efficiently to the RBD residues giving it the highest affinity with the lowest IC<sub>50</sub> value of 23.5 pM<ref name="Longxing">PMID:32907861</ref> (<scene name='10/1075251/Lcb1_binding_residues/3'>LCB1 and RBD binding residues</scene>). LCB3 was designed after LCB1 with the goal of making the minibinder even more efficient, however it ended up having a lower affinity than LCB1 with a higher IC<sub>50</sub> value of 40.1 pM<ref name="Longxing">PMID:32907861</ref> (<scene name='10/1075251/Lcb3_all/2'>LCB3 and RBD binding residues</scene>).
 The Glutamine-493 residue on the spike protein is an important residue in showing the differences in strength between ACE2 and the minibinders <ref name="Longxing">PMID:32907861</ref>. ACE2 does not make use of this residue when binding to the RBD. The nearest residues of ACE2, Gln35 and Lys31 do not form any interaction on Gln493 of the spike protein. The AHB2 minibinder, instead forms a Hydrogen bond on the Gln493 residue of the spike protein with its Glu41, increasing affinity to the spike protein. LCB1 forms two hydrogen bonds on Gln493 of the spike protein using two different residues, giving it the highest affinity based on the Gln493 residue. However, these interactions are not required. LCB1 forms no interactions with the Gln493 residue of the RDB previously mentioned, yet it still has a higher affinity to the RBD than AHB2 which forms a hydrogen bond with the Gln493 residue.