Modeling of the recognition site of the NK1 receptor

Svein Saebo, Elizabeth Keene, Tammy Fang, Bert C. Lynn, Rickey P. Hicks

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


The tachykinin receptor, NK1, and its native neuropeptide ligand, substance P, are believed to play a major role in the biochemistry of inflammation and in the transmission of pain. The binding of substance P is known to involve extracellular as well as transmembrane regions of the NK1 receptor. Reported here is the design of a model of the recognition site of the second transmembrane domain of the NK1 receptor. Molecular mechanics calculations were employed to evaluate the potential of six polypeptides corresponding to the first, second and third transmembrane domains of the NK1 receptor, to bind with substance P. One of the most promising of these models contained 30 amino acid residues corresponding to part of the first extracellular region coupled to the second transmembrane domain. A model of reduced size (18 amino acid residues) that contains the correct type and location of the amino acid residues predicted to be involved in ligand binding was used to validate the results of the molecular mechanics calculations. One-dimensional proton NMR spectra acquired in DMSO-d6 indicated that this 18 amino acid residue polypeptide forms a complex with substance P.

Original languageEnglish
Pages (from-to)65-77
Number of pages13
JournalJournal of Molecular Structure: THEOCHEM
Issue number1-2
StatePublished - Jul 31 1996

Bibliographical note

Funding Information:
This research was supported (in part) by the National Science Foundation EPSCoR Program (Grant EHR 91-08767),( NMR Facilities, Mississippi Magnetic Resonance Facility), National Science Foundation grant number, CHE-92124521, (Computer Facilities) National Science Foundation, grant number CHE-9205329, The State of Mississippi, and Mississippi State University.


  • Molecular mechanics calculation
  • Recognition site
  • Tachykinin receptor
  • Transmembrane domain

ASJC Scopus subject areas

  • Biochemistry
  • Condensed Matter Physics
  • Physical and Theoretical Chemistry


Dive into the research topics of 'Modeling of the recognition site of the NK1 receptor'. Together they form a unique fingerprint.

Cite this