Department of Chemistry, New York University, New York, New York 10003, USA.
J Chem Phys. 2012 Jul 14;137(2):024102. doi: 10.1063/1.4733389.
We propose a general framework for the efficient sampling of conformational equilibria in complex systems and the generation of associated free energy hypersurfaces in terms of a set of collective variables. The method is a strategic synthesis of the adiabatic free energy dynamics approach, previously introduced by us and others, and existing schemes using Gaussian-based adaptive bias potentials to disfavor previously visited regions. In addition, we suggest sampling the thermodynamic force instead of the probability density to reconstruct the free energy hypersurface. All these elements are combined into a robust extended phase-space formalism that can be easily incorporated into existing molecular dynamics packages. The unified scheme is shown to outperform both metadynamics and adiabatic free energy dynamics in generating two-dimensional free energy surfaces for several example cases including the alanine dipeptide in the gas and aqueous phases and the met-enkephalin oligopeptide. In addition, the method can efficiently generate higher dimensional free energy landscapes, which we demonstrate by calculating a four-dimensional surface in the Ramachandran angles of the gas-phase alanine tripeptide.
我们提出了一种通用框架，用于在复杂系统中有效采样构象平衡，并根据一组集体变量生成相关的自由能超曲面。该方法是我们和其他人之前提出的绝热自由能动力学方法与使用基于高斯的自适应偏置势来抑制先前访问区域的现有方案的战略综合。此外，我们建议采样热力学力而不是概率密度来重建自由能超曲面。所有这些元素都组合成一个稳健的扩展相空间形式，可轻松集成到现有的分子动力学软件包中。统一方案在为几个示例案例生成二维自由能表面方面优于元动力学和绝热自由能动力学，包括气相和水相中的丙氨酸二肽和 met-enkephalin 寡肽。此外，该方法可以有效地生成更高维的自由能景观，我们通过在气相丙氨酸三肽的 Ramachandran 角中计算一个四维表面来证明这一点。
