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

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来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，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，一个重大的缺点是在他们的时间尺度。 即使随着计算机能力的迅速发展，大多数模拟仍然限于几纳秒的真实的时间。 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。 Elber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，即原子级详细的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理解。 它们提供了关于探测器组在广泛的时间尺度上的运动的详细信息。 理想情况下，人们希望直接从MD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。 运动可以从简单的MD模拟中提取。 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，我们模拟自旋标记MTSSL结合半胱氨酸残基。 MD轨迹大约是5到10纳秒。 模拟包括明确的水溶剂化和长程静电相互作用的总和。氮氧自旋标签相对于磁场的取向已经从模拟使用时间平均值和不同轨迹的平均值计算。 结果产生了对重现光谱很重要的运动。关于这一点的第一篇论文已经发表在J. Phys. Chem.

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.