MOLECULAR DYNAMICS FLEXIBLE FITTING (MDFF)

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 冷冻电子显微镜提供了生物分子复合物在其功能状态下的密度图，但分辨率很低，不像X射线晶体学，它提供了生物分子的原子分辨率结构，但通常不是在生理状态下。联合收割机结合两种技术的信息的计算方法有望产生生理学上准确的、高分辨率的生物分子复合物结构。为了将来自这两个来源的联合收割机实验数据结合起来，该资源开发了一种新的方法，即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EM密度图中。MDFF采用分子动力学（MD）进行拟合，这允许灵活性，同时保持现实的构象。标准MD力场通过将EM密度图作为驱动原子进入高密度区域的吸引势来修改。此外，施加限制以保持生物分子的二级结构。MDFF的设置和分析是用资源的分子可视化程序VMD进行的，MDFF模拟是用资源的MD模拟软件NAMD进行的。由于NAMD具有高度可扩展性，并支持大型系统的模拟，因此MDFF可应用于大型大分子复合物，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].