Engineered Protein Inhibitors of SARS-CoV-2 Entry: Difference between revisions
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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='10/1075219/Lcb1/4'>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='10/1075219/Lcb3/5'>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='10/1075219/Lcb1/4'>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='10/1075219/Lcb3/5'>LCB3 binding</scene> reveals hydrogen bonding between D11 of the minibinder to K417 and R403 of the spike protein. | ||
[[Image:Comparison.jpeg|400 px|left|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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Furthermore, an interesting difference between the two design methods is the location of hydrogen bonding interactions. In AHB2, similar to ACE2, we see interactions spanning the entirety of the helices in contact with the spike protein. De novo design, on the other hand, reveals the main hydrogen bonding interactions occurring within the center residues of the helices. | Furthermore, an interesting difference between the two design methods is the location of hydrogen bonding interactions. In AHB2, similar to ACE2, we see interactions spanning the entirety of the helices in contact with the spike protein. De novo design, on the other hand, reveals the main hydrogen bonding interactions occurring within the center residues of the helices. | ||
Figure 4 shows the sequence comparison between the interacting helix of ACE2 and the helices of the three minibinders. | Figure 4 shows the sequence comparison between the interacting helix of ACE2 and the helices of the three minibinders. | ||
