IMPROVING CONFORMATIONAL SAMPLING IN SIMULATIONS OF BIOMOLECULES

我们的研究重点是提高工作效率的方法。 分子动力学(MD)中构象空间的采样 模拟。这种采样对于MD的许多应用是关键的， 具体包括(但不限于)计算免费 由化学或构象变化引起的能量差异 分子以及对分子三维结构的预测 生物分子。我们已经进行了模拟来计算 几种碳水化合物的反常自由能差 琥珀程序套件中提供的标准方法。目前， 我们正在实施本地增强抽样(LES)方法 Amber，并使用LES重复计算，确定 可获得的相对收益以及计算 在头顶上。此外，我们正在研究可能的方法来 提高分子动力学模拟预测分子构象的能力 溶液中的生物分子。大多数这样的预测都是严重的 受可能发生的有限构象采样的限制 在实惠的模拟过程中。因此，我们也实施了 LES方法进入琥珀的MD部分，我们目前正在运行 进行广泛的测试，以判断表现。我们单独使用LES 并与模拟退火法(SA)相结合，比较了两种算法的性能 从蛋白质环的模拟结果到由 常规的MD模拟。我们使用计算机图形学实验室 用于可视化我们的模拟结果。

Our research focuses on methods to increase the efficiency of the sampling of conformational space during molecular dynamics (MD) simulations. Such sampling is critical for many applications of MD, specifically including (but not limited to) the calculation of free energy differences due to chemical or conformational changes in a molecule as well as prediction of the three-dimensional structure of biological molecules. We have performed simulations to calculate the anomeric free energy differences for several carbohydrates using the standard methods available in the AMBER suite of programs. Currently, we are implementing the Locally Enhanced Sampling (LES) method in AMBER, and have repeated the calculations using LES, determining the relative benefits than can be obtained as well as the computational overhead. Additionally, we are investigating possible methods to improve the ability of MD simulations to predict the conformation of biological molecules in solution. Most such predictions are severely restricted by the limited conformational sampling that can occur during affordable simulations. we have therefore also implemented the LES method into the MD portion of AMBER, and we are currently running extensive tests to judge the performance. we are using LES both alone and in combination with Simulated Annealing (SA), comparing the results from simulations of protein loops to those obtained by conventional MD simulations. We use the Computer Graphics Laboratory for visualization of the results of our simulations.