(659g) Studying the Human Intestinal Mucin (Muc2) Using Molecular Modeling Approaches for Drug Transport Study Conference: AIChE Annual MeetingYear: 2006Proceeding: 2006 AIChE Annual MeetingGroup: Computational Molecular Science and Engineering ForumSession: Computational Biology: Membrane Phenomenology Time: Friday, November 17, 2006 - 2:18pm-2:36pm Authors: Sadasivan, V. D., Northeastern University Gulla, S., Northeastern University Sacco, Jr., A., Northeastern University Carrier, R. L., Northeastern University Intestinal mucus, a viscous secretion that lines the mucosa, is a major barrier to absorption of many therapeutic compounds. Nevertheless, there is as yet no clear understanding of the molecular interactions between drug molecules and the mucus membrane, and this barrier to drug transport is often largely overlooked. Secretory mucin, a large and complex glycoprotein molecule, is the principal determinants of the viscoelastic properties of intestinal mucus. Although mucin is known to play a significant role in inhibition of drug transport and in diseases such as Cystic Fibrosis, its structure remains mostly unknown. With the breakthrough of DNA sequencing through the human genome project, the major intestinal mucin gene, MUC2, has been identified and fully sequenced. Molecular modeling approaches along with Electron Spin Resonance (ESR) studies are being used to study molecular structure and intramolecular interactions of different regions of the MUC2 molecule. The terminal ends of MUC2 are rich in cysteine residues, and homology modeling is used as a tool to study these regions. Molecular dynamics is used to analyze the key tandem repeating sequence of MUC2, which is heavily glycosylated. In addition, ESR studies are also being performed to study the properties of hydrophobic and hydrophilic domains of mucin solutions using fatty acid spin probes, 16-doxylstearic acid (16-DSA) and 5-doxylstearic acid (5-DSA). Efforts to develop a molecular model of mucin have revealed a cysteine-knot tertiary structure at the carbon terminal end of MUC2 and interactions between hydrophobic probes and mucin solutions. Further model development will enable a greater understanding of molecular-level interactions influencing drug transport through mucus and how they are influenced by drug delivery agents.