title: Backbone conformations and side chain flexibility of two somatostatin mimics investigated by molecular dynamics simulations.
abstract: Molecular dynamics simulations with two designed somatostatin mimics, SOM230 and SMS 201-995, were performed in explicit water for a total aggregated time of 208 ns. Analysis of the runs with SOM230 revealed the presence of two clusters of conformations. Strikingly, the two sampled conformers correspond to the two main X-ray structures in the asymmetric unit of SMS 201-995. Structural comparison between the residues of SOM230 and SMS 201-995 provides an explanation for the high binding affinity of SOM230 to four of five somatostatin receptors. Similarly, cluster analysis of the simulations with SMS 201-995 shows that the backbone of the peptide interconverts between its two main crystallographic conformers. The conformations of SMS 201-995 sampled in the two clusters violated two different sets of NOE distance constraints in agreement with a previous NMR study. Differences in side chain fluctuations between SOM230 and SMS 201-995 observed in the simulations may contribute to the relatively higher binding affinity of SOM230 to most somatostatin receptors.
authors.affiliation: Department of Biochemistry, University of Zürich, Zürich, Switzerland. gianluca@u.washington.edu
authors.forename: Gianluca
authors.initials: G
authors.lastname: Interlandi
mesh_terms: D016000:Cluster Analysis; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D007700:Kinetics; D008958:Models, Molecular; D015282:Octreotide / Q000737:chemistry*; D011487:Protein Conformation; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000737:chemistry; D013696:Temperature; D013816:Thermodynamics; D013997:Time Factors
chemical_list: D013004:Somatostatin; C517782:pasireotide; D015282:Octreotide