Molecular dynamics (MD) simulations of VIP and PACAP27

Abstract

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide-27 (PACAP27) are members of the secretin-glucagon family containing 28 and 27 residues, respectively. NMR spectroscopy studies suggest that the N-terminus exhibit consecutive beta-turns whereas the central and C-terminal parts of the VIP molecule have been characterized as being two alpha-helices. In contrast, similar studies carried out on PACAP suggest that the shortest active peptide segment PACAP27 in the presence of trifluoroethanol (TFE) exhibits a disordered N-terminal domain followed by a alpha-helix expanding residues 9-26 with a discontinuity between residues 20 and 21. In the present study, a series of MD trajectories of VIP and PACAP27 were carried out using two different implicit models of the solvent: the Generalized Born that use an effective Born radii described by Onufriev, Bashford, and Case (GBOBC) and the Hawkins, Cramer, and Truhlar approximation (GBHCT) and two different force fields: AMBER ff99 and a modified version of the latter described by Sorin and Pande (Biophys J 2005, 88, 2472-2493), ff99SP. Comparison of the structures obtained from the MD trajectories and those derived from the NMR studies in the literature indicates that the GBOBC method is more efficient in the exploration of the conformational space and presents a higher agreement with the experimental structure of VIP and PACAP27 in TFE.

Folding Network of Villin Headpiece Subdomain

“…However, given the significantly reduced dimensionality of onedimensional (1D) profiles or smooth 2D landscapes, the roughness of the protein-folding landscape, and the heterogeneous nature of protein-folding pathways, it can be difficult to ascertain detailed and important features of protein folding from these simple representations (3). As more and more successful folding simulations are being reported (4)(5)(6)(7)(8)(9)(10)(11), it is becoming more urgent to find effective ways to present protein folding.…”

Neuroprotection of a Novel Cyclopeptide C*HSDGIC* from the Cyclization of PACAP (1–5) in Cellular and Rodent Models of Retinal Ganglion Cell Apoptosis

“…Structural analysis has shown that the N-terminus of PACAP (HSDGI) is flexible and disordered [21] , while C*HSDGIC* synthesized from cyclizing HSDGI and adding two Cys residues at both ends is more stable with a more fixed conformation. Furthermore, CHC has a small molecular weight (approximately 700 Da), which allows it to easily penetrate the blood-retina barrier.…”

Emerging Methods for Ensemble-Based Virtual Screening

“…The implicit solvent approach essentially reduces solvent friction and has been shown to enhance conformational sampling for a wide variety of peptide, protein, and nucleic acid systems [95–97], and more recently, larger protein systems [98, 99]. Correspondence between GB models and experimentally derived structures has also been established [100, 101], which, similar to AMD, makes it a good choice for extensions of the computational receptor ensemble.…”