Figure 1: Sample groups from the CADseek Shape Analytics Report for the Protein Data Bank (PDB).
Ames, Iowa – October 14, 2022 - iSEEK Corporation, the Market Leader in Shape Search, posted the Protein Data Bank (PDB) CADseek Shape Analytics Report on 3DShapeIndex.com. The 3D shape similarity analysis was performed on a total of 114,448 3D protein models. The CADseek 3D Shape Analytics Engine generated 35,988 similar 3D shape protein groupings in 13 minutes on a 4-core i7 workstation using a minimum CADseek Shape Similarity Score of 89%.
For example, Group-14641 in the CADseek Shape Analytics Report, Figure 2, matched the 3D shape of PDB3q5p, the crystal structure of bacterial multidrug resistance regulator (BmrR) bound to the Antibiotic Tetracycline, to the 3D shape of PDB3Q5R, the crystal structure of bacterial multidrug resistance regulator (BmrR) bound to the antibiotic Kanamycin, at a CADseek 3D Shape Similarity Score of 97.45%.
Figure 2: Group-14641 in the CADseek 3D Shape Analytics Report for the Protein Data Bank (PDB).
To explain Group-14642 in the CADseek Shape Analytics Report, Figure 3, it is important first to understand nucleocytoplasmic transport: the translocation of macromolecules into the nucleus. Nucleocytoplasmic transport is a fundamental process for regulating gene expression as well as cell division and differentiation. This process is mediated by the importin{alpha} adaptor protein that literally “carries” the macromolecules by providing two potential binding locations for them: a major binding site and a minor binding site. For example, PDB3q5u and PDB3knd proteins have been known to bind to the minor binding site on the importin{alpha} adaptor protein but with weak affinity. And the paper by Chang, C.-W., Couñago, R.M., Williams, S.J., Bodén, M. and Kobe, B. (2013), Distinctive Conformation of Minor Site-Specific Nuclear Localization Signals Bound to Importin-α. [Traffic, 14: 1144-1154. https://doi.org/10.1111/tra.12098], used crystallographic and biochemical methods to demonstrate that the following proteins: PDB3zip, PDB3zio, PDB3ziq, PDB3zir, and PDB3zin, will bind on the minor binding site on importin{alpha}.
Figure 3: Group-14642 in the CADseek 3D Shape Analytics Report for the Protein Data Bank (PDB).
Group-14642 in the CADseek Shape Analytics Report matched the 3D shape of PDB3q5u, to the following 3D protein structures: PDB4oih, PDB3zip, PDB5v5p, PDB3zio, PDB2ynr, PDB6wbb, PDB6wbc, PDB3ziq, PDB6iw8, PDB5huy, PDB3zir, PDB3tpo, PDB3knd, PDB4mz5, PDB3tpm, and PDB3zin in a CADseek Shape Similarity Score range from 97.45% to 93.40%, Figure 3. The CADseek Shape Analytics Report grouped the proteins proven by crystallographic and biochemical methods to bind on the minor binding site on importin{alpha} only using the CADseek Shape Similarity Score between their 3D structures and that of PDB3q5u; a protein known to bind to the minor binding site on importin{alpha}.
To explain Group-14643 in the CADseek Shape Analytics Report, Figure 4, it is important first to understand Antisense technology: the selective inhibition of protein synthesis at the nucleic acid level. The antisense nucleic acid sequence base pairs with its complementary sense RNA strands to prevent it from being translated into a protein that would be needed for the disease to progress. Antisense technology is used successfully in the treatment of viral infections and cancers.
Figure 4: Group-14643 in the CADseek 3D Shape Analytics Report for the Protein Data Bank (PDB).
Group-14643 in the CADseek Shape Analytics Report used PDB3q61 as the target 3D structure to identify other proteins in the PDB with similar 3D structures. PDB3q61 is 3'-Fluoro Hexitol Nucleic Acid DNA. The CADseek 3D Shape Analytics Report matched the 3D shape of PDB3q61 to PDB3v07 and PDB3oz5 at CADseek Shape Similarity Scores of 95.94% and 93.67%, respectively. PDB3v07 is the Crystal structure of R-6'-Me-3'-Fluoro Hexitol Nucleic Acid, while PDB3oz5 is the S-Methyl Carbocyclic Locked Nucleic Acid Analogues. Locked Nucleic Acid is a novel type of nucleic acid analog.
In addition to posting the full CADseek 3D Shape Analytics Report for the Protein Data Bank (PDB) on 3DShapeIndex.com, the iSEEK Corporation – the Market Leader in Shape Search, also offers the downloadable application iSEEK3D on 3DShapeIndex.com to allow the user to issue 3D shape search requests against the set of 114,448 3D protein models indexed on 3DShapeIndex.com as well as other 3D models from 3D Datasets available on the web. iSEEK3D applies iSEEK Corporation’s CADseek shape coding algorithms to generate a shape signature locally on the user’s computer. It is mathematically impossible to reverse engineer the 3D geometry from its shape signature. The iSEEK3D application sends the shape signature to the 3DShapeIndex cloud platform as a shape search target to find similar shapes. Shape search results are returned from 3DShapeIndex for the user to review within their iSEEK3D application.