ABCB1 p.Ser658Arg
| Predicted by SNAP2: | A: N (82%), C: N (72%), D: N (78%), E: N (87%), F: N (82%), G: N (82%), H: N (87%), I: N (78%), K: N (87%), L: N (82%), M: N (87%), N: N (93%), P: N (78%), Q: N (87%), R: N (87%), T: N (93%), V: N (82%), W: N (57%), Y: N (82%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, T: N, V: N, W: N, Y: N, |
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[hide] In silico model for P-glycoprotein substrate predi... J Comput Aided Mol Des. 2013 Apr;27(4):347-63. doi: 10.1007/s10822-013-9650-x. Epub 2013 Apr 24. Prajapati R, Singh U, Patil A, Khomane KS, Bagul P, Bansal AK, Sangamwar AT
In silico model for P-glycoprotein substrate prediction: insights from molecular dynamics and in vitro studies.
J Comput Aided Mol Des. 2013 Apr;27(4):347-63. doi: 10.1007/s10822-013-9650-x. Epub 2013 Apr 24., [PMID:23612916]
Abstract [show]
P-glycoprotein (P-gp) is a plasma membrane efflux transporter belonging to ATP-binding cassette superfamily, responsible for multidrug resistance in tumor cells. Over-expression of P-gp in cancer cells limits the efficacy of many anticancer drugs. A clear understanding of P-gp substrate binding will be advantageous in early drug discovery process. However, substrate poly-specificity of P-gp is a limiting factor in rational drug design. In this investigation, we report a dynamic trans-membrane model of P-gp that accurately identified the substrate binding residues of known anticancer agents. The study included homology modeling of human P-gp based on the crystal structure of C. elegans P-gp, molecular docking, molecular dynamics analyses and binding free energy calculations. The model was further utilized to speculate substrate propensity of in-house anticancer compounds. The model demonstrated promising results with one anticancer compound (NSC745689). As per our observations, the molecule could be a potential lead for anticancer agents devoid of P-gp mediated multiple drug resistance. The in silico results were further validated experimentally using Caco-2 cell lines studies, where NSC745689 exhibited poor permeability (P app 1.03 +/- 0.16 x 10(-6) cm/s) and low efflux ratio of 0.26.
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No. Sentence Comment
197 The secondary structure prediction from HMMTOP and SAMT02 servers showed helical structure from Thr 627 to Glu 636 and Ser 658 to Arg 666 in linker region.
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ABCB1 p.Ser658Arg 23612916:197:119
status: NEW