LONG TIME DYNAMICS OF BIOMOLECULES: COMPARISON OF MOLECULAR DYNAMICS & ESR

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。 生物分子的分子动力学(MD)模拟大大增加了我们对其功能的理解。然而，一个重大缺陷是它们的时间尺度。即使在计算机能力快速增长的情况下，大多数模拟仍然限于几纳秒的实时。这个时间域太短了，无法研究许多生物物理过程，如蛋白质的构象转变和蛋白质折叠。埃尔伯一直在开发一种替代方法，以探索更长的时间尺度。另一种方法保持了MD的优点，即图像原子详细，适用范围广。EPR实验丰富了我们对蛋白质动力学的理解。它们提供了关于探测组在广泛的时间范围内运动的详细信息。理想情况下，人们希望直接从分子动力学模拟计算ESR谱。自旋的取向动力学与分子运动相耦合，使得探测特定的大分子运动成为可能。运动可以从直接的MD模拟中提取出来。我们还计划进行中间计算，其中来自MD模拟的信息将丰富唯象理论。我们正在研究蛋白质溶菌酶。在我们的MD研究中，我们模拟了与半胱氨酸残基结合的自旋标记MTSSL。MD的轨迹大约是5到10纳秒。模拟包括显式水溶剂化和长程静电相互作用的总和。使用时间平均值和不同轨迹上的平均值从模拟中计算了氮氧化物自旋标记相对于磁场的取向。结果产生了对重现光谱很重要的运动。这方面的第一篇psper已经发表在《物理杂志》上。化学。

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. Molecular dynamics (MD) simulations of biological molecules add considerably to our understanding of their function. Nevertheless, a significant drawback is in their time scales. Even with the rapid growth in computer power, most simulations are still limited to a few nanoseconds of real time. This time domain is far too short to study many biophysical processes, such as conformational transitions in proteins, and protein folding. Elber has been developing an alternative approach to explore significantly more extended time scales. The alternative approach maintains the advantages of MD an atomically detailed picture, and wide applicability. EPR experiments enrich our understanding of protein dynamics. They provide detailed information on the motions of probe groups on a wide range of time scales. Ideally, one would like to compute ESR spectra directly from MD simulations. The orientation dynamics of the spin is coupled to molecular motions and makes it possible to probe specific macromolecular motions. The motions can be extracted from straightforward MD simulations. We also plan to perform intermediate computations in which information from MD simulations will enrich the phenomenological theories. We are investigating the protein lysozyme. In our MD studies we model the spin label MTSSL that binds to cysteine residues. The MD trajectories are about five to ten nanoseconds. The simulations include explicit water solvation and summation of long-range electrostatic interactions. The orientation of the nitroxide spin label with respect to the magnetic field have been computed from the simulation using time averages and averages over different trajectories. The results are yielding the motions important to reproduce the spectra. A first psper on this has been published in J. Phys. Chem.