Abstract
A conformational search for the most probable structures of the hormone α-MSH in aqueous solution was performed in order to help determine the structural features necessary for biological activity. The free-energy surface was modeled using methods from integral equation theory, and high- temperature molecular dynamics was used to enhance conformational sampling. Families of low free-energy structures have been found. The minimum energy structure shows a stable β-turn conformation in the putative message region that is stabilized by a salt bridge between Glu5 and Lys11. The orientation of the side chains reflects the amphophilic nature of the peptide, and a close interaction between the side chains of the His6, Phe7 and Trp9 was observed. Several structural features observed in the minimum energy structure agree well with experimental results. The conformational features led to a hypothesis of a receptor-hormone interaction model in which the hydrophobic side chains of Phe7 and Trp9 interact with the transmembrane portion of the human melanocortin (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 language | English (US) |
|---|---|
| Pages (from-to) | 394-407 |
| Number of pages | 14 |
| Journal | Journal of Peptide Research |
| Volume | 54 |
| Issue number | 5 |
| DOIs | |
| State | Published - 1999 |
| Externally published | Yes |
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Keywords
- Integral equations
- Peptides
- Potentials of mean force
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
Cite this
Modeling of α-MSH conformations with implicit solvent. / Prabhu, N. V.; Perkyns, J. S.; Pettitt, Bernard.
In: Journal of Peptide Research, Vol. 54, No. 5, 1999, p. 394-407.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Modeling of α-MSH conformations with implicit solvent
AU - Prabhu, N. V.
AU - Perkyns, J. S.
AU - Pettitt, Bernard
PY - 1999
Y1 - 1999
N2 - A conformational search for the most probable structures of the hormone α-MSH in aqueous solution was performed in order to help determine the structural features necessary for biological activity. The free-energy surface was modeled using methods from integral equation theory, and high- temperature molecular dynamics was used to enhance conformational sampling. Families of low free-energy structures have been found. The minimum energy structure shows a stable β-turn conformation in the putative message region that is stabilized by a salt bridge between Glu5 and Lys11. The orientation of the side chains reflects the amphophilic nature of the peptide, and a close interaction between the side chains of the His6, Phe7 and Trp9 was observed. Several structural features observed in the minimum energy structure agree well with experimental results. The conformational features led to a hypothesis of a receptor-hormone interaction model in which the hydrophobic side chains of Phe7 and Trp9 interact with the transmembrane portion of the human melanocortin (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.
AB - A conformational search for the most probable structures of the hormone α-MSH in aqueous solution was performed in order to help determine the structural features necessary for biological activity. The free-energy surface was modeled using methods from integral equation theory, and high- temperature molecular dynamics was used to enhance conformational sampling. Families of low free-energy structures have been found. The minimum energy structure shows a stable β-turn conformation in the putative message region that is stabilized by a salt bridge between Glu5 and Lys11. The orientation of the side chains reflects the amphophilic nature of the peptide, and a close interaction between the side chains of the His6, Phe7 and Trp9 was observed. Several structural features observed in the minimum energy structure agree well with experimental results. The conformational features led to a hypothesis of a receptor-hormone interaction model in which the hydrophobic side chains of Phe7 and Trp9 interact with the transmembrane portion of the human melanocortin (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.
KW - Integral equations
KW - Peptides
KW - Potentials of mean force
UR - http://www.scopus.com/inward/record.url?scp=0032723820&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032723820&partnerID=8YFLogxK
U2 - 10.1034/j.1399-3011.1999.00113.x
DO - 10.1034/j.1399-3011.1999.00113.x
M3 - Article
C2 - 10563505
AN - SCOPUS:0032723820
VL - 54
SP - 394
EP - 407
JO - Chemical Biology and Drug Design
JF - Chemical Biology and Drug Design
SN - 1747-0277
IS - 5
ER -