Journal of
Bioinformatics and Sequence Analysis

  • Abbreviation: J. Bioinform. Seq. Anal.
  • Language: English
  • ISSN: 2141-2464
  • DOI: 10.5897/JBSA
  • Start Year: 2009
  • Published Articles: 45

Full Length Research Paper

Molecular docking of human histamine H1 receptor with chlorpheniramine to alleviate cat allergies

Uma Maheshwari

  •  Accepted: 22 October 2010
  •  Published: 28 January 2011

Abstract

 

Cat allergen Fel d 1, secreted by the cat’s sebaceous glands and that covers the cat’s skin and fur is the major cat allergen responsible for cat allergies in human. It interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine from the mast cell or basophil. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction and also increases vascular permeability and potentiates pain. Chlorpheniramine is a histamine H1 antagonist of the alkyl amine class. It competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It binds to the histamine H1 receptor and blocks the action of endogenous histamine there by providing effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies. Homology modeling of Histamine H1 Receptor is done using SWISSPDBVIEWER – SWISSMODEL. It showed 27 helices, 6 strands and 37 turns. The stereochemistry of the theoretical model of Histamine H1 Receptor is studied by subjecting it into energy minimization in SWISSPDBVIEWER. The model was subjected to structure verification and evaluation using PROCHECK. The Ramachandran plot for the model showed 92.5% residues in most favored regions and hence the model was revealed to have good stereo chemistry. A molecular docking study of modeled structure of Histamine H1 Receptor with the drug chlorpheniramine is done using PatchDock program. Receptor–Drug complex has a complementarity score of 4846, Atomic Contact Energy (ACE) of -139.35. The docking studies which involves the interaction of Histamine H1 Receptor with the drug chlorpheniramine provided valuable insight into the role of chlorpheniramine having anti histamine activity and in alleviating cat allergies produced by the cat allergen namely Fel d 1 protein.

 

Key words: Fel d 1 protein, cat allergy, histamine H1 receptor, chlorpheniramine, SWISSPDBVIEWER, SWISSMODEL, PROCHECK, PatchDock, homology modeling, molecular docking, receptor-drug complex.