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Using Confocal Analysis of Xenopus laevis to Investigate Modulators of Wnt and Shh Morphogen Gradients
Published on: December 14, 2015
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Structural dynamics and inhibitor searching for Wnt-4 protein using comparative computational studies.
Mirza A Hammad1, Syed Sikander Azam1
1National Center for Bioinformatics, Quaid-i-Azam University, Islamabad, Pakistan.
Drug Design, Development and Therapy
|May 22, 2015
Summary
This study identifies novel inhibitors targeting Wnt-4 protein and its bound palmitoleic acid to block aberrant activity. These findings offer new therapeutic strategies for Wnt-4-associated cancers.
Area of Science:
- Molecular Biology
- Biochemistry
- Computational Chemistry
Background:
- Wnt-4 protein is vital for embryonic development.
- Aberrant Wnt-4 activity is linked to gastric, colon, and breast cancers.
- Wnt proteins share a conserved structural fold.
Purpose of the Study:
- To identify potent inhibitors of Wnt-4.
- To develop inhibitors that target both Wnt-4 protein and its bound acyl group.
- To inhibit aberrant Wnt-4 activity and its associated anomalies.
Main Methods:
- Computational analysis including docking of palmitoleic acid into Wnt-4.
- Large-scale virtual screening of over 200,000 compounds.
- Comparative docking using GOLD, AutoDock-Vina, and FRED.
Main Results:
- Identified lead inhibitors with maximum interactions to Wnt-4 and bound palmitoleic acid.
- Palmitoleic acid is crucial for Wnt-4 activity.
- Aberrant Wnt-4 expression can be effectively inhibited.
Conclusions:
- Developed a systematic computational approach for Wnt-4 inhibitor discovery.
- Selected lead compounds represent promising therapeutic candidates.
- Targeting both Wnt-4 protein and palmitoleic acid is a viable strategy for cancer treatment.
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