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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。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，一个显著的缺点是它们的时间尺度。即使随着计算机能力的快速发展，大多数模拟仍然被限制在几纳秒的实时时间内。这个时间域太短，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。埃尔伯一直在开发另一种方法来探索更长的时间尺度。另一种方法保留了MD的优点，即原子细节图像和广泛的适用性。EPR实验丰富了我们对蛋白质动力学的认识。它们提供了探测器群在大范围时间尺度上运动的详细信息。理想情况下，人们希望直接从MD模拟中计算ESR谱。自旋的取向动力学与分子运动耦合，使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模拟的信息将丰富现象学理论。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签MTSSL。MD轨迹大约是5到10纳秒。模拟包括显式水溶剂化和远程静电相互作用的总和。利用时间平均值和不同轨迹上的平均值，计算了氮氧化物自旋标签相对于磁场的取向。结果产生了对重现光谱很重要的运动。这方面的第一篇论文发表在《J. Phys》杂志上

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