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Design of a Three Dimensional Physical Model of P‐glycoprotein
Author(s) -
Colton Shan,
Herman Tim,
Giles Kurt,
Koo Ben,
Jeske Sabine,
Grover Anita,
Gin Richard
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.699.12
Subject(s) - p glycoprotein , small molecule , transporter , efflux , drug , drug discovery , computational biology , chemistry , mechanism (biology) , computer science , nanotechnology , biophysics , pharmacology , biochemistry , medicine , physics , materials science , biology , gene , multiple drug resistance , quantum mechanics , antibiotics
Expressed in a large variety of tissues, the transporter P‐glycoprotein (P‐gp) facilitates small molecule efflux from cells as a detoxification mechanism for a remarkable range of drug substrates. Of interest to clinicians and drug development scientists is the number of drug‐drug interactions mediated by competitive inhibition of the protein. Similarly, as it is highly expressed in enterocytes, P‐gp can be a significant barrier to drug absorption, and, therefore, considerable effort has been spent on the discovery of a non‐absorbed P‐gp inhibitor. Traditional methods for visualizing protein structures and interactions with small molecules are limited in the amount of information that can be conveyed in two dimensions. Using rapid prototyping technology, we have built tangible 3D models of P‐gp using the recently resolved structure (PDB: 3g5u), allowing students and scientists alike to more fully explore the transporter protein and its small molecule substrates and inhibitors. The SMART (Students Modeling A Research Topic) program was established by theCenter of BioMolecular Modeling at the Milwaukee School of Engineering and involves partnerships between university researchers and local high schools. This work is funded by NIH‐NCRR‐SEPA and HHMI.