Engineered Protein Inhibitors of SARS-CoV-2 Entry: Difference between revisions

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The first design method, Rosetta, created AHB2 based on the single interacting helix of ACE2. With <scene name='10/1078124/Ahb2/1'>AHB2 binding</scene>, we see two alpha helices mimicking ACE2. Hydrogen bonding interactions between N36, D11, K43, E41, and E30 of the minibinder interact with residues K417, R403, Y449, Q493, and N487, respectively, in the spike protein.  
The first design method, Rosetta, created AHB2 based on the single interacting helix of ACE2. With <scene name='10/1078124/Ahb2/1'>AHB2 binding</scene>, we see two alpha helices mimicking ACE2. Hydrogen bonding interactions between N36, D11, K43, E41, and E30 of the minibinder interact with residues K417, R403, Y449, Q493, and N487, respectively, in the spike protein.  
 
[[Image:Comparison.jpeg|400 px|right|thumb|Figure 4: The sequence differences between ACE2, AHB2, LCB1 and LCB3.]]
De novo designed proteins, as discussed previously, focused on computational design to determine residues best able to interact with the spike protein. We will focus on LCB1 and LCB3. <scene name='10/1078124/Lcb1/1'>LCB1 binding</scene> reveals hydrogen bonding between D30 of the minibinder and both K417 and R403 of the spike protein, in addition to D17 and R14 of the minibinder interacting with Q493 of the spike protein. Similarly, <scene name='10/1078124/Lcb3/1'>LCB3 binding</scene> reveals hydrogen bonding between D11 of the minibinder to K417 and R403 of the spike protein.  
De novo designed proteins, as discussed previously, focused on computational design to determine residues best able to interact with the spike protein. We will focus on LCB1 and LCB3. <scene name='10/1078124/Lcb1/1'>LCB1 binding</scene> reveals hydrogen bonding between D30 of the minibinder and both K417 and R403 of the spike protein, in addition to D17 and R14 of the minibinder interacting with Q493 of the spike protein. Similarly, <scene name='10/1078124/Lcb3/1'>LCB3 binding</scene> reveals hydrogen bonding between D11 of the minibinder to K417 and R403 of the spike protein.  
[[Image:Comparison.jpeg|400 px|right|thumb|Figure 4: The sequence differences between ACE2, AHB2, LCB1 and LCB3.]]


Within all four binding sites, we see two conserved residues throughout: K417 and Q493. This finding reveals the importance of these residues in both binding and stability.  
Within all four binding sites, we see two conserved residues throughout: K417 and Q493. This finding reveals the importance of these residues in both binding and stability.  
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