Mode matches in hydrophobic free energy eigenfunctions predict peptide- protein interactions

A. J. Mandell, M. J. Owens, K. A. Selz, W. N. Morgan, M. F. Shlesinger, Charles Nemeroff

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The dominant statistical hydrophobic free energy inverse frequencies, amino acid wavelengths as hydrophobic modes, of neurotensin (NT), cholescystokinin (CCK), the human dopamine D2 receptor [(DA)D2], and the human dopamine transporter (DAT) were determined using orthogonal decomposition of the autocovariance matrices of their amino acid sequences as hydrophobic free energy equivalents in kcal/mol. The leading eigenvalues- associated eigenvectors were convolved with the original series to construct eigenfunctions. Eigenfunctions were further analyzed using discrete trigonometric wavelet and all poles, maximum entropy power spectral transformations. This yielded clean representations of the dominant hydrophobic free energy modes, most of which are otherwise lost in the smoothing of hydropathy plots or contaminated by end effects and multimodality in conventional Fourier transformations. Mode matches were found between NT and (DA)D2 and between CCK and DAT, but not the converse. These mode matches successfully predicted the nonlinear kinetic interactions of NT-(DA)D2 in contrast with CCK-(DA)D2 on 3H-spiperone binding to (DA)D2, and by CCK-DAT but not NT-DAT on [N-methyl-3H]-WIN 35,428 binding to DAT in (DA)D2 and DAT cDNA stably transfected cell lines without known NT or CCK receptors. Computation of the dominant modes of hydrophobic free energy eigenfunctions may help predict functionally relevant peptide-membrane protein interactions, even across neurotransmitter families.

Original languageEnglish
Pages (from-to)89-101
Number of pages13
JournalBiopolymers
Volume46
Issue number2
DOIs
StatePublished - Aug 1 1998
Externally publishedYes

Fingerprint

Dopamine Plasma Membrane Transport Proteins
Neurotensin
Eigenvalues and eigenfunctions
Peptides
Free energy
Proteins
Amino acids
Amino Acids
Spiperone
Entropy
Neurotransmitter Agents
Dopamine
Amino Acid Sequence
Poles
Membrane Proteins
Complementary DNA
Cells
Decomposition
Cell Line
Wavelength

Keywords

  • Cholecystokinin
  • Dopamine D receptor
  • Dopamine transporter (DAT)
  • Hydrophobic free energy eigenfunction
  • Hydrophobic modes
  • Neurotensin
  • Peptide hydrophobic wavelets
  • Peptide power spectra

ASJC Scopus subject areas

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

Cite this

Mode matches in hydrophobic free energy eigenfunctions predict peptide- protein interactions. / Mandell, A. J.; Owens, M. J.; Selz, K. A.; Morgan, W. N.; Shlesinger, M. F.; Nemeroff, Charles.

In: Biopolymers, Vol. 46, No. 2, 01.08.1998, p. 89-101.

Research output: Contribution to journalArticle

Mandell, A. J. ; Owens, M. J. ; Selz, K. A. ; Morgan, W. N. ; Shlesinger, M. F. ; Nemeroff, Charles. / Mode matches in hydrophobic free energy eigenfunctions predict peptide- protein interactions. In: Biopolymers. 1998 ; Vol. 46, No. 2. pp. 89-101.
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