To determine free energy surfaces along chosen reaction coordinates is an important and challenging task in simulating complex systems. In this thesis we develop two techniques to enhance sampling: one is mass scaling; another is repository based adaptive umbrella sampling (RBAUS).;Scaling the atomic mass can enhance the sampling efficiency. By making the atomic masses more equal, the reduction of the frequencies of fastest motions will allow a lengthening of the time step. Our results showed that increasing the hydrogen mass to 10 amu would allow a time step of 3 fs in ab initio QM/MM BO-MD simulations and lead to little change in the simulated free energy profiles and structural properties in comparison with corresponding simulations using 1 fs time step and the normal mass.;More importantly, we developed RBAUS method and two further extensions. In this new adaptive sampling approach, a sampling repository is periodically updated based on the latest simulation data, and the accumulated knowledge and sampling history are then employed to determine whether and how to update the biasing umbrella potential for subsequent simulations. In comparison with other adaptive methods, a unique and attractive feature of the RBAUS approach is that the frequency for updating the biasing potential depends on the sampling history and is adaptively determined on the fly, which makes it possible to smoothly bridge non-equilibrium and quasi-equilibrium simulations. By introducing sampling entropy and concentration theorem into the biasing potential updating scheme, the second version of RBAUS has the significantly improved adaptivity, robustness and applicability. In the third version of RBAUS, the biasing potential updating is based on the Bayesian inference, which better describes the biasing potential.;The RBAUS methods are first tested by simulations on two simple systems: a double well model system with a variety of barriers and the dissociation of a NaCl molecule in water. Their efficiency and applicability are further illustrated in ab initio QM/MM MD simulations of a methyl-transfer reaction in aqueous solution and determining two dimensional free energy surfaces of alanine dipeptide in gas phase and in water.
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机译：在模拟复杂系统中，确定沿所选反应坐标的自由能表面是一项重要且具有挑战性的任务。在本文中，我们开发了两种增强采样的技术：一种是质量缩放；另一种是质量缩放。另一个是基于存储库的自适应伞式采样（RBAUS）。缩放原子质量可以提高采样效率。通过使原子质量更相等，最快运动频率的降低将允许时间步长的延长。我们的结果表明，将氢质量增加到10 amu，从头开始的QM / MM BO-MD模拟将允许3 fs的时间步，与使用1的相应模拟相比，模拟的自由能分布和结构特性几乎没有变化。 fs时间步长和正常质量。更重要的是，我们开发了RBAUS方法和两个进一步的扩展。在这种新的自适应采样方法中，将根据最新的模拟数据定期更新采样存储库，然后使用累积的知识和采样历史来确定是否以及如何为后续的模拟更新偏置伞势。与其他自适应方法相比，RBAUS方法的独特和吸引人之处在于，用于更新偏置电位的频率取决于采样历史记录，并且可以实时确定，这使得平滑平衡非平衡和准平衡成为可能。平衡模拟。通过将采样熵和集中定理引入到偏电势更新方案中，第二版的RBAUS具有显着提高的适应性，鲁棒性和适用性。在RBAUS的第三个版本中，偏置电势的更新基于贝叶斯推断，它可以更好地描述偏置电势。RBAUS方法首先通过在两个简单系统上的仿真进行了测试：具有多种障碍的双井模型系统；以及NaCl分子在水中的离解。它们的效率和适用性在水溶液中甲基转移反应的从头开始的QM / MM MD模拟中以及在气相和水中确定丙氨酸二肽的二维自由能表面时得到了进一步说明。
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