Scuola Normale Superiore, Piazza dei Cavalieri 7, 56126 Pisa, Italy.
Phys Chem Chem Phys. 2019 Sep 18;21(36):19921-19934. doi: 10.1039/c9cp03557e.
The search for stationary points in the molecular potential energy surfaces (PES) is a problem of increasing relevance in different fields of molecular sciences especially for large, flexible systems characterized by several large-amplitude internal motions leading to shallow minima with comparable energies and separated by small barriers. After structural biology and medicinal chemistry, also high-resolution molecular spectroscopy, which is the focus of our research activity, is nowadays shifting its attention to this kind of molecular systems. In such circumstances, accurate geometrical structures and relative stabilities of all these minima are a mandatory prerequisite for the vis-à-vis comparison between computed and experimental spectra. This task raises, in turn, the problem of the best compromise between accuracy and feasibility. In our opinion, a promising route is offered by a two-level stochastic search in which a relatively inexpensive MM or QM method is used in the initial search, followed by single point energy evaluation at a higher QM level of a relatively large number of low-energy structures in order to select a final short-list of candidates, whose geometries are fully optimized at the higher QM level. Finally, the relative stabilities and properties of the final short-list of energy minima can be computed by a state-of-the-art QM approach. This strategy defines a general two-level search/three-level evaluation approach, which can be finely tuned in terms of the accuracy of the sought results. Setup of the procedure, interface with a general purpose electronic structure code and validation of the most effective low-level methods for some representative molecular systems (three already well characterized and one new) ended up with a general, robust and user-friendly tool, which can be easily used and extended also by non-specialists to aid experimental spectroscopic studies.
在分子势能表面（PES）中寻找稳定点是分子科学不同领域中越来越重要的问题，特别是对于具有多个大振幅内运动的大、柔性系统，这些内运动会导致能量相近且被小势垒隔开的浅势阱。在结构生物学和药物化学之后，目前也将注意力转向这种分子系统的高分辨率分子光谱学。在这种情况下，所有这些势阱的准确几何结构和相对稳定性是对计算和实验光谱进行相对比较的强制性前提。这一任务反过来又提出了在准确性和可行性之间取得最佳折衷的问题。在我们看来，一种有前途的方法是两级随机搜索，其中相对廉价的 MM 或 QM 方法用于初始搜索，然后在相对较高的 QM 水平上对相对大量的低能结构进行单点能量评估，以选择最终的短名单候选者，其几何形状在较高的 QM 水平上完全优化。最后，可以通过最先进的 QM 方法计算最终短名单能量势阱的相对稳定性和性质。这种策略定义了一种通用的两级搜索/三级评估方法，可以根据所寻求结果的准确性进行精细调整。该程序的设置、与通用电子结构代码的接口以及一些代表性分子系统（三个已经很好地描述的和一个新的）的最有效低水平方法的验证最终得到了一个通用、健壮且用户友好的工具，即使是非专家也可以轻松使用和扩展该工具，以帮助实验光谱学研究。
