MOLECULAR DYNAMICS FLEXIBLE FITTING (MDFF)

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 与X射线结晶学不同，低温电子显微镜提供了处于功能状态的生物分子化合物的密度图，但分辨率较低，而X射线结晶学提供了生物分子的原子分辨率结构，但通常不处于生理状态。将这两种技术的信息结合起来的计算方法有望产生生理上准确的、高分辨率的生物分子复合体结构。为了将这两个来源的实验数据结合起来，资源开发了一种新的方法--分子动力学灵活拟合(MDFF；http://www.ks.uiuc.edu/Research/mdff)[1，2])，以将原子结构拟合到低温电子密度图中。MDFF使用分子动力学(MD)来进行拟合，这使得在保持真实构象的同时具有灵活性。通过将EM密度图作为吸引势来修改标准MD力场，从而将原子驱动到高密度区域。此外，还应用限制条件来保存生物分子的二级结构。MDFF设置和分析使用资源的分子可视化程序VMD执行，MDFF模拟使用资源的MD模拟软件NAMD进行。由于NAMD具有高度的可扩展性并支持大系统的模拟，MDFF可应用于大分子复合体，如核糖体[3]。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cryo-electron microscopy provides density maps of biomolecular complexes in theirfunctional states, but only at low resolution, unlike X-ray crystallography, whichprovides atomic-resolution structures of biomolecules but usually not in a physiologicalstate. Computational methods to combine information from both techniqueshold the promise of generating physiologically accurate, high-resolution structuresof biomolecular complexes. To combine experimental data from these two sources,the Resource developed a novel method, molecular dynamics flexible fitting (MDFF;http://www.ks.uiuc.edu/Research/mdff) [1,2], to fit atomic structures into cryo-EMdensity maps. MDFF employs molecular dynamics (MD) to perform the fitting,which allows flexibility while maintaining a realistic conformation. The standardMD force field is modified by incorporating the EM density map as an attractivepotential that drives atoms into high-density regions. Furthermore, restraints are applied to preserve secondary structure of the biomolecules. MDFF setup and analysisare performed with the Resource's molecular visualization program, VMD, andMDFF simulations are conducted using the Resource's MD simulation software,NAMD. Since NAMD is highly scalable and supports simulation of large systems,MDFF can be applied to large macromolecular complexes such as the ribosome [3].