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Backbone conformations and side chain flexibility of two somatostatin mimics investigated by molecular dynamics simulations
Author(s) -
Interlandi Gianluca
Publication year - 2008
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22277
Subject(s) - somatostatin , molecular dynamics , chemistry , conformational isomerism , somatostatin analogue , flexibility (engineering) , side chain , molecule , computational chemistry , mathematics , biology , endocrinology , octreotide , statistics , organic chemistry , polymer
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. Proteins 2009. © 2008 Wiley‐Liss, Inc.