Structure and dynamics of α-MSH using DRISM integral equation theory and stochastic dynamics

Ninad V. Prabhu, John S. Perkyns, Bernard Pettitt, Victor J. Hruby

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The structural and dynamical features of the hormone α-MSH in solution have been examined over a 100 ns time scale by using free energy molecular mechanics models at room temperature. The free energy surface has been modeled using methods from integral equation theory and the dynamics by the Langevin equation. A modification of the accessible surface area friction drag model was used to calculate the atomic friction coefficients. The molecule shows a stable β-turn conformation in the message region and a close interaction between the side chains of His6, Phe7, and Trp9. A salt bridge between Glu5 and Arg8 was found not to be a preferred interaction, whereas a Glu5 and Lys11 salt bridge was not sampled, presumably due to relatively high free energy barriers. The message region was more conformationally rigid than the N-terminal region. Several structural features observed here agree well with experimental results. The conformational features suggest a receptor-hormone interaction model where the hydrophobic side chains of Phe7 and Trp9 interact with the transmembrane portion of the MC1 receptor. Also, the positively charged side chain of Arg8 and the imidazole side chain of His6 may interact with the negatively charged portions of the receptor which may even be on the receptor's extracellular loops.

Original languageEnglish (US)
Pages (from-to)255-272
Number of pages18
JournalBiopolymers
Volume50
Issue number3
DOIs
StatePublished - Sep 1999
Externally publishedYes

Fingerprint

Melanocyte-Stimulating Hormones
Friction
Free energy
Integral equations
Salts
Receptor, Melanocortin, Type 1
Hormones
Molecular Models
Mechanics
Hydrophobic and Hydrophilic Interactions
Molecular mechanics
Energy barriers
Temperature
Drag
Conformations
Molecules
imidazole

Keywords

  • Diffusion coefficient
  • DRISM
  • Friction coefficient
  • Integral equation
  • MSH
  • Peptide conformation
  • Solution structure
  • Stochastic dynamics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Biophysics

Cite this

Structure and dynamics of α-MSH using DRISM integral equation theory and stochastic dynamics. / Prabhu, Ninad V.; Perkyns, John S.; Pettitt, Bernard; Hruby, Victor J.

In: Biopolymers, Vol. 50, No. 3, 09.1999, p. 255-272.

Research output: Contribution to journalArticle

Prabhu, Ninad V. ; Perkyns, John S. ; Pettitt, Bernard ; Hruby, Victor J. / Structure and dynamics of α-MSH using DRISM integral equation theory and stochastic dynamics. In: Biopolymers. 1999 ; Vol. 50, No. 3. pp. 255-272.
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