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 language | English |
|---|---|
| Pages (from-to) | 89-101 |
| Number of pages | 13 |
| Journal | Biopolymers |
| Volume | 46 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 1 1998 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Mode matches in hydrophobic free energy eigenfunctions predict peptide- protein interactions
AU - Mandell, A. J.
AU - Owens, M. J.
AU - Selz, K. A.
AU - Morgan, W. N.
AU - Shlesinger, M. F.
AU - Nemeroff, Charles
PY - 1998/8/1
Y1 - 1998/8/1
N2 - 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.
AB - 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.
KW - Cholecystokinin
KW - Dopamine D receptor
KW - Dopamine transporter (DAT)
KW - Hydrophobic free energy eigenfunction
KW - Hydrophobic modes
KW - Neurotensin
KW - Peptide hydrophobic wavelets
KW - Peptide power spectra
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UR - http://www.scopus.com/inward/citedby.url?scp=0032145022&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1097-0282(199808)46:2<89::AID-BIP4>3.0.CO;2-T
DO - 10.1002/(SICI)1097-0282(199808)46:2<89::AID-BIP4>3.0.CO;2-T
M3 - Article
C2 - 9664843
AN - SCOPUS:0032145022
VL - 46
SP - 89
EP - 101
JO - Biopolymers - Peptide Science Section
JF - Biopolymers - Peptide Science Section
SN - 0006-3525
IS - 2
ER -