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的密度图， 功能状态，但只有在低分辨率，不像X射线晶体学， 提供了生物分子的原子分辨率结构，但通常不是在生理上。 状态两种技术的联合收割机信息的计算方法 有望产生生理上准确的高分辨率结构， 生物分子复合物的。为了将来自这两个来源的实验数据联合收割机， 该资源开发了一种新的方法，分子动力学柔性拟合（MDFF; http：//www.ks.uiuc.edu/Research/mdff）[1，2]，以将原子结构拟合到cryo-EM中 密度图MDFF采用分子动力学（MD）来执行拟合， 其允许柔性同时保持真实的构造。标准 MD力场是通过将EM密度图作为一个有吸引力的 驱动原子进入高密度区域的势能。此外，还施加限制以保持二级结构 的生物分子。MDFF设置和分析 使用资源的分子可视化程序VMD进行， MDFF模拟使用资源的MD模拟软件进行， NAMD。由于NAMD具有高度可扩展性并支持大型系统的仿真， MDFF可以应用于大分子复合物，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 their functional states, but only at low resolution, unlike X-ray crystallography, which provides atomic-resolution structures of biomolecules but usually not in a physiological state. Computational methods to combine information from both techniques hold the promise of generating physiologically accurate, high-resolution structures of 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-EM density maps. MDFF employs molecular dynamics (MD) to perform the fitting, which allows flexibility while maintaining a realistic conformation. The standard MD force field is modified by incorporating the EM density map as an attractive potential that drives atoms into high-density regions. Furthermore, restraints are applied to preserve secondary structure of the biomolecules. MDFF setup and analysis are performed with the Resource's molecular visualization program, VMD, and MDFF 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].