ISSN:
0948-5023
Keywords:
Keywords: neurophysin/dipeptide complex, peptide ligand interactions, association, molecular dynamics
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract The nonapeptide hormones oxytocin (OT) and vasopressin (VP), while transported in the posterior pituitary, are packaged into neurosecretory granules (NSG) in the form of high associates with disulfide-rich proteins known as neurophysin I (NPI) and neurophysin II (NPII), respectively. In the NSG, neurophysins serve as carrier proteins to the hormones, until the latter are dissociated upon secretion into blood. To shed more light on molecular self-recognition between NPs, and between NPs and their ligands, we have studied their molecular association, using as a starting point the recently published solid-state structure (Cα-trace) of the neurophysin II-dipeptide complex. Another purpose of this work was the development of reliable strategies for molecular modeling, that would utilize minimal structural information (like Cα-trace and/or structural homology) yet be useful for studies of protein/ligand interactions. An initial all-atom representation of the protein-peptide complex (2:2) was obtained by the conversion of the Cα-carbon trace deposited in the Brookhaven Protein Data Bank (file 1BN2), using the InsightII/Biopolymer modules from the suite of programs supplied by Biosym Technologies, San Diego. The free NPII homodimer was obtained by removal of the dipeptide ligands from the starting structures. Both associates, after initial immersion in water, were submitted to gradual (side chains first then all atoms) minimization of energy. Subsequently, they were thermally equilibrated and submitted to the molecular dynamics (AMBER 4.0) at 300K, until the total energy was stabilized. The structures, averaged over the last 20 ps of the dynamics, were compared with the starting Cα-trace and among themselves. The protein/ligand complex, simulated in water, compares favorably with the solid-state reference. An allosteric mechanism for the NPII dimer/ligand interaction is proposed and discussed.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s008940050011
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