...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >On the use of low-frequency normal modes to enforce collective movements in refining macromolecular structural models
【24h】

On the use of low-frequency normal modes to enforce collective movements in refining macromolecular structural models

机译：关于在细化大分子结构模型中使用低频法向模式强制集体运动

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

As more and more structures of macromolecular complexes get solved indifferent conditions, it has become apparent that flexibility is an inherent part of their biological function. Normal mode analysis using simplified models of proteins such as the elastic network model has proved very effective in showing that many of the structural transitions derived from a survey of the Protein Data Bank can be explained by just a few of the lowest-frequency normal modes. In this work, normal modes are used to carry out medium- or low-resolution structural refinement, enforcing collective and large-amplitude movements that are beyond the reach of existing methods. Refinement is carried out in reciprocal space with respect to the normal mode amplitudes, by using standard conjugate-gradient minimization. Several tests on synthetic diffraction data whose mode concentration follows the one of real movements observed in the Protein Data Bank have shown that the radius of convergence is larger than the one of rigid-body refinement. Tests with experimental diffraction data for the same protein in different environments also led to refined structural models showing drastic reduction of the rms deviation with the target model. Because the structural transition is described by very few parameters, over-fitting of real experimental data is easily detected by using a cross-validation test. The method has also been applied to the refinement of atomic models into molecular envelopes and could readily be used to fit large macromolecular complex rearrangements into cryo-electron microscopy-reconstructed images as well as small-angle x-ray scattering-derived envelopes.
机译：随着越来越多的大分子复合物的结构在不同条件下得到解决，很明显，柔韧性是其生物学功能的固有部分。使用简化的蛋白质模型（例如弹性网络模型）进行的正常模式分析已被证明非常有效，它表明从蛋白质数据库进行的调查得出的许多结构转变只能由最低频率的正常模式来解释。在这项工作中，正常模式用于执行中分辨率或低分辨率的结构改进，从而实现了现有方法无法实现的集体和大幅度运动。通过使用标准的共轭梯度最小化，在相对于正常模式振幅的倒数空间中进行细化。对合成衍射数据进行的多项测试（其模式浓度遵循蛋白质数据库中观察到的真实运动之一）显示，会聚半径大于刚体精细化的收敛半径。使用不同环境中相同蛋白质的实验衍射数据进行的测试还导致精炼的结构模型显示出与目标模型相比均方根偏差的大幅降低。由于结构转换是由很少的参数来描述的，因此通过使用交叉验证测试，很容易检测到实际实验数据的过度拟合。该方法也已应用于将原子模型精化为分子包膜，并且可以很容易地用于将大分子复杂的重排装配到冷冻电子显微镜重建的图像以及小角度X射线散射得到的包膜中。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号