ABCB1 p.Val34Ala
| Predicted by SNAP2: | A: D (63%), C: D (63%), D: D (85%), E: D (80%), F: D (63%), G: D (75%), H: D (80%), I: N (82%), K: D (80%), L: D (63%), M: D (53%), N: D (80%), P: D (80%), Q: D (71%), R: D (80%), S: D (66%), T: D (66%), W: D (75%), Y: D (71%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, L: N, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, W: D, Y: D, |
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[hide] Homology modelling and molecular docking of MDR1 w... Biomed Pharmacother. 2015 Apr;71:37-45. doi: 10.1016/j.biopha.2015.02.009. Epub 2015 Feb 19. Subhani S, Jayaraman A, Jamil K
Homology modelling and molecular docking of MDR1 with chemotherapeutic agents in non-small cell lung cancer.
Biomed Pharmacother. 2015 Apr;71:37-45. doi: 10.1016/j.biopha.2015.02.009. Epub 2015 Feb 19., [PMID:25960213]
Abstract [show]
MDR1, a protein commonly involved in drug transport, has been linked to multi drug resistance and disease progression in cancers such as non-small cell lung cancer. Hence, targeting this protein is essential for improving drug design and preventing adverse drug-drug interactions. The aim of the study was to examine chemotherapeutic drug binding to MDR1 and the interactions therein. We have used Schrodinger suite 2014, to perform homology modelling of human MDR1 based on Mouse MDR1, followed by Induced Fit Docking with Paclitaxel, Docetaxel, Gemcitabine, Carboplatin and Cisplatin drugs. Finally, we evaluated drug binding affinities using Prime/MMGBSA and using these scores we compared the affinities of combination therapies against MDR1. Analysis of the docking results showed Paclitaxel>Docetaxel>Gemcitabine>Carboplatin>Cisplatin as the order of binding affinities, with Paclitaxel having the best docking score. The combination drug binding affinity analysis showed Paclitaxel+Gemcitabine to have the best docking score and hence, efficacy. Through our investigation we have identified the residues Gln 195 and Gln 946 to be more frequently involved in drug binding interactions with MDR1. Our results suggest that, Paclitaxel or combination of Paclitaxel+Gemcitabine could serve as a suitable therapy against MDR1 in NSCLC patients. Thus, our study provides new insight into the possible repurposing of chemotherapeutic drugs in targeting elevated MDR1 levels in NSCLC patients, thereby ensuring better overall outcome. Further our study highlights the use of in silico methodologies in understanding drug binding to protein targets and its relevance to advancing lung cancer therapy.
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No. Sentence Comment
42 The amino acids from Val 34 to Ala 1275 of Human MDR1 were only used for modelling since the corresponding template co-ordinates are available only for this region.
X
ABCB1 p.Val34Ala 25960213:42:21
status: NEW109 Residues from Val 34-Ala 1275 were used for modelling.
X
ABCB1 p.Val34Ala 25960213:109:14
status: NEW