Sandbox Reserved 1848

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Revision as of 03:21, 15 April 2025

This Sandbox is Reserved from March 18 through September 1, 2025 for use in the course CH462 Biochemistry II taught by R. Jeremy Johnson and Mark Macbeth at the Butler University, Indianapolis, USA. This reservation includes Sandbox Reserved 1828 through Sandbox Reserved 1846.

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You may include any references to papers as in: the use of JSmol in Proteopedia ^[1] or to the article describing Jmol ^[2] to the rescue.

1 Function
2 example/sandbox section
- 2.1 meow
3 image and green links
4 ref
5 end
6 Disease
7 Relevance
8 Structural highlights

Function

example/sandbox section

meow

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D30 residue

Figure 1

Image of D30 on LCB1 attached to spike

ref

^[3] Reference meow meow meow ^[3] short ref

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Structural highlights

The goal of designing these minibinders was to create a molecule with a higher binding affinity with the RBD than ACE2, meaning they had to be designed with specific residues that form stronger connections with the same binding pockets that ACE2 would bind to^[4]. This section highlights some important residue differences between the minibinders and ACE2 that give the minibinders a higher affinity.

The glutamine-493 (Q493) residue is an important residue in showing the differences in strength between ACE2 and the minibinders^[4]. ACE2 doesn’t make use of this residue when binding to the RBD, the nearest residues, Glu-35 and Lys-31 don’t form any interaction with Q493. Comparing this to the AHB2 minibinder, which forms a Hydrogen bond with the Q493 residue, the AHB2 minibinder makes better use of the RBD’s residue than ACE2, helping it have a higher affinity to the spike protein. LCB1 makes even better use of the Q493 residue, forming two hydrogen bonds with two different residues, giving it the highest affinity based on the Q493 residue.

Another important binding site on the RBD includes the Lysine-417 (K417) and Arginine-403 (R403) residues. While ACE2 does form a hydrogen bond interaction with the K417 residue using its own D30 residue, LCB1 forms H bond interactions with both of them, using its own D30 residue, forming a very strong interaction that is hard to break.

It is important to note that these highlighted residues aren’t the only residues that differ between the minibinders, and it is a compilation of all the residue interactions that give each minibinder different affinities. For example, LCB1 forms no interactions with the Q493 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 Q493 residue^[4].

The goal of designing these minibinders was to create a molecule with a higher binding affinity with the RDB than ACE2, meaning they had to be designed with specific residues that form stronger connections with the same residues that ACE2 would bind to. This section highlights some important residue differences between the minibinders and ACE2 that give the minibinders a higher affinity.

The glutamine-493 (Q493) residue is an important residue in showing the differences in strength between ACE2 and the minibinders. ACE2 doesn’t make use of this residue when binding to the RBD, the nearest residues, Glu-35 and Lys-31 don’t form any interaction with Q493. Comparing this to the AHB2 minibinder, which forms a Hydrogen bond with the Q493 residue, the AHB2 minibinder makes better use of the RDB’s residue than ACE2, helping it have a higher affinity to the spike protein. LCB1 makes even better use of the Q493 residue, forming two hydrogen bonds with two different residues, giving it the highest affinity based on the Q493 residue.

Another important binding site on the RDB includes the Lysine-417 (K417) and Arginine-403 (R403) residues. While ACE2 does form a hydrogen bond interaction with the K417 residue using its own D30 residue, LCB1 forms H bond interactions with both of them, using its own D30 residue, forming a very strong interaction that is hard to break.

It is important to note that these highlighted residues aren’t the only residues that differ between the minibinders, and it is a compilation of all the residue interactions that give each minibinder different affinities. For example, LCB1 forms no interactions with the Q493 residue of the RDB previously mentioned, yet it still has a higher affinity to the RDB than AHB2 which forms a hydrogen bond with the Q493 residue.

This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

References

↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
↑ ^3.0 ^3.1 Ransey E, Paredes E, Dey SK, Das SR, Heroux A, Macbeth MR. Crystal structure of the Entamoeba histolytica RNA lariat debranching enzyme EhDbr1 reveals a catalytic Zn(2+) /Mn(2+) heterobinucleation. FEBS Lett. 2017 Jul;591(13):2003-2010. doi: 10.1002/1873-3468.12677. Epub 2017, Jun 14. PMID:28504306 doi:http://dx.doi.org/10.1002/1873-3468.12677
↑ ^4.0 ^4.1 ^4.2 Cao L, Goreshnik I, Coventry B, Case JB, Miller L, Kozodoy L, Chen RE, Carter L, Walls AC, Park YJ, Strauch EM, Stewart L, Diamond MS, Veesler D, Baker D. De novo design of picomolar SARS-CoV-2 miniprotein inhibitors. Science. 2020 Oct 23;370(6515):426-431. PMID:32907861 doi:10.1126/science.abd9909

Retrieved from "http://52.214.119.220/wiki/index.php/Sandbox_Reserved_1848"

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 == Structural highlights ==
-The differences in the minibinders' efficacy can be explained using the IC50 which represents the concentration of the minibinder needed to inhibit the ACE2 binding to the spike protein, meaning the lower IC50, the better. LCB1, LCB3, and AHB2, were the minibinders with the lowest IC50 values with LCB1 having the lowest of all of them.
+The goal of designing these minibinders was to create a molecule with a higher binding affinity with the RBD than ACE2, meaning they had to be designed with specific residues that form stronger connections with the same binding pockets that ACE2 would bind to<ref name="Longxing">PMID:32907861</ref>. This section highlights some important residue differences between the minibinders and ACE2 that give the minibinders a higher affinity.
+The glutamine-493 (Q493) residue is an important residue in showing the differences in strength between ACE2 and the minibinders<ref name="Longxing">PMID:32907861</ref>. ACE2 doesn’t make use of this residue when binding to the RBD, the nearest residues, Glu-35 and Lys-31 don’t form any interaction with Q493. Comparing this to the AHB2 minibinder, which forms a Hydrogen bond with the Q493 residue, the AHB2 minibinder makes better use of the RBD’s residue than ACE2, helping it have a higher affinity to the spike protein. LCB1 makes even better use of the Q493 residue, forming two hydrogen bonds with two different residues, giving it the highest affinity based on the Q493 residue.
+Another important binding site on the RBD includes the Lysine-417 (K417) and Arginine-403 (R403) residues. While ACE2 does form a hydrogen bond interaction with the K417 residue using its own D30 residue, LCB1 forms H bond interactions with both of them, using its own D30 residue, forming a very strong interaction that is hard to break.
+It is important to note that these highlighted residues aren’t the only residues that differ between the minibinders, and it is a compilation of all the residue interactions that give each minibinder different affinities. For example, LCB1 forms no interactions with the Q493 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 Q493 residue<ref name="Longxing">PMID:32907861</ref>.
+The goal of designing these minibinders was to create a molecule with a higher binding affinity with the RDB than ACE2, meaning they had to be designed with specific residues that form stronger connections with the same residues that ACE2 would bind to. This section highlights some important residue differences between the minibinders and ACE2 that give the minibinders a higher affinity.
+The glutamine-493 (Q493) residue is an important residue in showing the differences in strength between ACE2 and the minibinders. ACE2 doesn’t make use of this residue when binding to the RBD, the nearest residues, Glu-35 and Lys-31 don’t form any interaction with Q493. Comparing this to the AHB2 minibinder, which forms a Hydrogen bond with the Q493 residue, the AHB2 minibinder makes better use of the RDB’s residue than ACE2, helping it have a higher affinity to the spike protein. LCB1 makes even better use of the Q493 residue, forming two hydrogen bonds with two different residues, giving it the highest affinity based on the Q493 residue.
+Another important binding site on the RDB includes the Lysine-417 (K417) and Arginine-403 (R403) residues. While ACE2 does form a hydrogen bond interaction with the K417 residue using its own D30 residue, LCB1 forms H bond interactions with both of them, using its own D30 residue, forming a very strong interaction that is hard to break.
+It is important to note that these highlighted residues aren’t the only residues that differ between the minibinders, and it is a compilation of all the residue interactions that give each minibinder different affinities. For example, LCB1 forms no interactions with the Q493 residue of the RDB previously mentioned, yet it still has a higher affinity to the RDB than AHB2 which forms a hydrogen bond with the Q493 residue.
 This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

Sandbox Reserved 1848

From Proteopedia

Revision as of 03:21, 15 April 2025

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