Academia.eduAcademia.edu

Figure 1 – uploaded by Estari Mamidala

See full PDFdownloadDownload figure
Based on the analysis of the key active site residues Glu283, Phe109, Tyr108, Trp86, Tyr37, Tyr251, and Tyr89, the compound 4-deoxywithperuvin exhibits the most favorable interactions compared to the other two ligands, including the standard drug Maraviroc. 4-deoxywithperuvin forms a critical hydrogen bond with the essential Glu283 residue, in addition to engaging in van der Waals contacts with Phe109, Tyr108, Trp86, Tyr37, and Tyr251 - all of which are crucial for stabilizing the ligand- receptor complex. In contrast, the other compound, 14-alpha,17-beta-dihydroxy-withanolide, lacks direct hydrogen bonding with the active site residues, although it still demonstrates van der Waals interactions with Tyr89, Tyr108, and Trp86. Maraviroc, the standard drug, also shows van der Waals contacts with some of the active site residues, but it too lacks the critical hydrogen bonding observed with 4-deoxywithperuvin. Overall, the superior binding of 4-deoxywithperuvin, as evidenced by its hydrogen bonding and extensive interactions with the key active site residues, suggests it may be the most promising candidate among the three for further development as a potential CCRS5 inhibitor. 1411 Phe:109, Ile:198, Gln:194, Asn:163, Phe:182, Leu:255, Tyr:251, 108, Met:279, 287, Glu:283, Trp:86, Thr:284, and Tyr:37. While Maraviroc does not form any direct hydrogen bond interactions, its binding energy and the nature of the interactions suggest that it is a reasonable benchmark for comparison against the other two ligands.

Table 1 Based on the analysis of the key active site residues Glu283, Phe109, Tyr108, Trp86, Tyr37, Tyr251, and Tyr89, the compound 4-deoxywithperuvin exhibits the most favorable interactions compared to the other two ligands, including the standard drug Maraviroc. 4-deoxywithperuvin forms a critical hydrogen bond with the essential Glu283 residue, in addition to engaging in van der Waals contacts with Phe109, Tyr108, Trp86, Tyr37, and Tyr251 - all of which are crucial for stabilizing the ligand- receptor complex. In contrast, the other compound, 14-alpha,17-beta-dihydroxy-withanolide, lacks direct hydrogen bonding with the active site residues, although it still demonstrates van der Waals interactions with Tyr89, Tyr108, and Trp86. Maraviroc, the standard drug, also shows van der Waals contacts with some of the active site residues, but it too lacks the critical hydrogen bonding observed with 4-deoxywithperuvin. Overall, the superior binding of 4-deoxywithperuvin, as evidenced by its hydrogen bonding and extensive interactions with the key active site residues, suggests it may be the most promising candidate among the three for further development as a potential CCRS5 inhibitor. 1411 Phe:109, Ile:198, Gln:194, Asn:163, Phe:182, Leu:255, Tyr:251, 108, Met:279, 287, Glu:283, Trp:86, Thr:284, and Tyr:37. While Maraviroc does not form any direct hydrogen bond interactions, its binding energy and the nature of the interactions suggest that it is a reasonable benchmark for comparison against the other two ligands.

Related Figures (6)

Figure-1. The 3D crystal structure of CCR5 (PDB ID: 4MBS shown in cartoon representation. IDENTIFYING PROMISING CCR5-DIRECTED LEADS FROM WITHANIASOMNIFERA FOR HIV-1 MANAGEMENT VIA COMPUTATIONAL MOLECULAR DOCKING TECHNIQUES
Figure-1. The 3D crystal structure of CCR5 (PDB ID: 4MBS shown in cartoon representation. IDENTIFYING PROMISING CCR5-DIRECTED LEADS FROM WITHANIASOMNIFERA FOR HIV-1 MANAGEMENT VIA COMPUTATIONAL MOLECULAR DOCKING TECHNIQUES
IDENTIFYING PROMISING CCR5-DIRECTED LEADS FROM WITHANIASOMNIFERA FOR HIV-1 MANAGEMENT VIA COMPUTATIONAL MOLECULAR DOCKING TECHNIQUES
IDENTIFYING PROMISING CCR5-DIRECTED LEADS FROM WITHANIASOMNIFERA FOR HIV-1 MANAGEMENT VIA COMPUTATIONAL MOLECULAR DOCKING TECHNIQUES
ee ND IE EI. PIE IEEE PN IDE IEE IEEE II IEEE IEEE III IIE IIE IEDE IIE EIDE OEE ID This ligand has a lower binding energy of -8.41 kcal/mol compared to 4-deoxywithperuvin, but it still exhibits a good affinity for the CCRS5 receptor. Unlike the previous ligand, 14-alpha,17-beta- dihydroxy-withanolide does not form any hydrogen bond interactions. Instead, its binding is primarily driven by hydro phobic and van der Waals interactions with surrounding residues, including His:175, Gln:93, Ala:92, Lys:26, Leu:33, Ala:29, Tyr:89, Ala:90, Tyr:108, Thr:177, Tyr:37, and Trp:86. While the lack of hydrogen bonding may suggest a slightly less stable ligand-receptor complex, the compound's favorable binding energy still makes it a viable candidate for further exploration.
ee ND IE EI. PIE IEEE PN IDE IEE IEEE II IEEE IEEE III IIE IIE IEDE IIE EIDE OEE ID This ligand has a lower binding energy of -8.41 kcal/mol compared to 4-deoxywithperuvin, but it still exhibits a good affinity for the CCRS5 receptor. Unlike the previous ligand, 14-alpha,17-beta- dihydroxy-withanolide does not form any hydrogen bond interactions. Instead, its binding is primarily driven by hydro phobic and van der Waals interactions with surrounding residues, including His:175, Gln:93, Ala:92, Lys:26, Leu:33, Ala:29, Tyr:89, Ala:90, Tyr:108, Thr:177, Tyr:37, and Trp:86. While the lack of hydrogen bonding may suggest a slightly less stable ligand-receptor complex, the compound's favorable binding energy still makes it a viable candidate for further exploration.
Figure-4. 2D and Three-dimensional schematic interaction between CCR5 (PDB: 4MBS) and Maraviroc (Standard drug). Balls and sticksrepresent amino acid residues and ligands, respectively. Green dashed lines indicate hydrogen bonds. Pink and purpledashed lines indicate hydrophobic bonds
Figure-4. 2D and Three-dimensional schematic interaction between CCR5 (PDB: 4MBS) and Maraviroc (Standard drug). Balls and sticksrepresent amino acid residues and ligands, respectively. Green dashed lines indicate hydrogen bonds. Pink and purpledashed lines indicate hydrophobic bonds
Related topics:
BioinformaticsBiology
580 California St., Suite 400
San Francisco, CA, 94104
© 2025 Academia. All rights reserved