Backbone conformations and side chain flexibility of two somatostatin mimics investigated by molecular dynamics simulations
Backbone conformations and side chain flexibility of two somatostatin mimics investigated by molecular dynamics simulations
复制标题
DOI：
10.1002/prot.22277
复制
发表时间：
2009-05-15
影响因子：
2.9
通讯作者：
Interlandi, Gianluca
中科院分区：
文献类型：
--
作者：
Interlandi, Gianluca
用设计的两种生长抑素模拟物SOM230和SMS 201-995在显水中进行分子动力学模拟，总聚合时间为208 ns。用SOM230进行分析，发现存在两组构象。引人注目的是，这两个采样的构象对应于SMS 201-995不对称单元中的两个主要x射线结构。SOM230和SMS 201-995残基之间的结构比较解释了SOM230与5种生长抑素受体中的4种具有高结合亲和力的原因。同样，用SMS 201-995进行的聚类分析表明，肽的主链在其两个主要的晶体构象之间相互转换。在两个簇中采样的SMS 201-995的构象违反了两组不同的NOE距离约束，这与先前的NMR研究一致。模拟中观察到的SOM230和SMS 201-995之间侧链波动的差异可能有助于SOM230对大多数生长抑素受体的相对较高的结合亲和力。
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.