Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two neuropeptides, substance P (SP) and SP-tyrosine-8 (SP-Y8), have been studied by molecular dynamics (MD) simulation in a TIP3P water/CCl4 biphasic solvent system as a mimic for the water-membrane system. Initially, distance restraints derived from NMR nuclear Overhauser enhancements (NOE) were incorporated in the restrained MD (RMD) in the equilibration stage of the simulation. The starting orientation/position of the peptides for the MD simulation was either parallel to the water/CCl4 interface or in a perpendicular/insertion mode. In both cases the peptides equilibrated and adopted a near-parallel orientation within approximately 250 ps. After equilibration, the conformation and orientation of the peptides, the solvation of both the backbone and the side chain of the residues, hydrogen bonding, and the dynamics of the peptides were analyzed from trajectories obtained in the RMD or the subsequent free MD (where the NOE restraints were removed). These analyses showed that the peptide backbone of nearly all residues are either solvated by water or are hydrogen-bonded. This is seen to be an important factor against the insertion mode of interaction. Most of the interactions with the hydrophobic phase come from the hydrophobic interactions of the side chains of Pro-4, Phe-7, Phe-8, Leu-10, and Met-11 for SP, and Phe-7, Leu-10, Met-11 and, to a lesser extent, Tyr-8 in SP-Y8. Concerted conformational transitions took place in the time frame of hundreds of picoseconds. The concertedness of the transition was due to the tendency of the peptide to maintain the necessary secondary structure to position the peptide properly with respect to the water/CCl4 interface.
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PMID:Molecular dynamics study of substance P peptides in a biphasic membrane mimic. 1004 5

Two neuropeptides, substance P (SP) and SP-tyrosine-8 (SP-Y8), have been studied by molecular dynamics (MD) simulation in an explicit sodium dodecylsulfate (SDS) micelle. Initially, distance restraints derived from NMR nuclear Overhauser enhancements (NOE) were incorporated in the restrained MD (RMD) during the equilibration stage of the simulation. It was shown that when SP-Y8 was initially placed in an insertion (perpendicular) configuration, the peptide equilibrated to a surface-bound (parallel) configuration in approximately 450 ps. After equilibration, the conformation and orientation of the peptides, the solvation of both the backbone and the side chain of the residues, hydrogen bonding, and the dynamics of the peptides were analyzed from trajectories obtained from the RMD or the subsequent free MD (where the NOE restraints were removed). These analyses showed that the peptide backbones of all residues are either solvated by water or are hydrogen-bonded. This is seen to be an important factor against the insertion mode of interaction. Most of the interactions come from the hydrophobic interaction between the side chains of Lys-3, Pro-4, Phe-7, Phe-8, Leu-10, and Met-11 for SP, from Lys-3, Phe-7, Leu-10, and Met-11 in SP-Y8, and the micellar interior. Significant interactions, electrostatic and hydrogen bonding, between the N-terminal residues, Arg-Pro-Lys, and the micellar headgroups were observed. These latter interactions served to affect both the structure and, especially, the flexibility, of the N-terminus. The results from simulation of the same peptides in a water/CCl4 biphasic cell were compared with the results of the present study, and the validity of using the biphasic system as an approximation for peptide-micelle or peptide-bilayer systems is discussed.
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PMID:Molecular dynamics study of substance P peptides partitioned in a sodium dodecylsulfate micelle. 1004 6