In silico binding mechanism prediction of benzimidazole based corticotropin releasing factor-1 receptor antagonists by quantitative structure activity relationship, molecular docking and pharmacokinetic parameters calculation

Journal of Biomolecular Structure & Dynamics
Neeraj KumarSourav Kalra

Abstract

Despite the various research efforts toward the treatment of stress-related disorders, the drug has not yet launched last 20 years. Corticotropin releasing factor-1 receptor antagonists have been point of great interest in stress-related disorders. In the present study, we have selected benzazole scaffold-based compounds as corticotropin releasing factor-1 antagonists and performed 2D and 3D QSAR studies to identify the structural features to elucidating the binding mechanism prediction. The best 2D QSAR model was obtained through multiple linear regression method with r2 value of .7390, q2 value of .5136 and pred_r2 (predicted square correlation coefficient) value of .88. The contribution of 2D descriptor, T_2_C_1 was 60% (negative contribution) and 4pathClusterCount was 40.24% (positive contribution) in enhancing the activity. Also 3D QSAR model was statistically significant with q2 value of .9419 and q2_se (standard error of internal validation) value of .19. Statistical parameters results prove the robustness and significance of both models. Further, molecular docking and pharmacokinetic analysis was performed to explore the scope of investigation. Docking results revealed that the all benzazole compounds show hydrogen bond...Continue Reading

References

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Methods Mentioned

BETA
MDS

Software Mentioned

VLife Molecular Design Suite (
LigPrep
VLife MDS
MM
VLifeMDS
Maestro
SWkNN
4pathClusterCount
VLife
QikProp

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