BACKGROUND Dramatic progress has recently been made in cryo-electron microscopy technologies, which now make possible the reconstruction of a growing number of biomolecular structures to near-atomic resolution. However, the need persists for fitting and refinement approaches that address those cases that require modeling assistance. METHODS In this paper, we describe algorithms to optimize the performance of such medium-resolution refinement methods. These algorithms aim to automatically optimize the parameters that define the density shape of the flexibly fitted model, as well as the time-dependent damper cutoff distance. Atomic distance constraints can be prescribed for cases where extra containment of parts of the structure is helpful, such as in regions where the density map is poorly defined. Also, we propose a simple stopping criterion that estimates the probable onset of overfitting during the simulation. RESULTS The new set of algorithms produce more accurate fitting and refinement results, and yield a faster rate of convergence of the trajectory toward the fitted conformation. The latter is also more reliable due to the overfitting warning provided to the user. CONCLUSIONS The algorithms described here were implemented in the new Damped-Dynamics Flexible Fitting simulation tool "DDforge" in the Situs package.

中文翻译：

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使用阻尼动力学，针对中分辨率冷冻电磁图对原子模型进行精确灵活的细化。

背景技术近来，在冷冻电子显微镜技术上已经取得了巨大的进步，这使得将越来越多的生物分子结构重建到接近原子分辨率成为可能。但是，仍然需要适合那些需要建模协助的情况的拟合和优化方法。方法在本文中，我们描述了优化此类中等分辨率优化方法性能的算法。这些算法旨在自动优化定义柔性拟合模型的密度形状的参数以及与时间有关的阻尼器截止距离。可以规定原子距离约束条件，以用于对结构的各个部分进行额外控制，例如在密度图定义不明确的区域。也，我们提出了一个简单的停止准则，该准则用于估计模拟期间过拟合的可能开始。结果新的算法集产生更准确的拟合和优化结果，并使轨迹朝着拟合构象的收敛速度更快。由于提供给用户的过度安装警告，后者也更加可靠。结论本文所述的算法已在Situs软件包中的新型阻尼动态拟合仿真工具“ DDforge”中实现。由于提供给用户的过度安装警告，后者也更加可靠。结论本文所述的算法已在Situs软件包中的新型阻尼动态拟合仿真工具“ DDforge”中实现。由于提供给用户的过度安装警告，后者也更加可靠。结论本文所述的算法已在Situs软件包中的新型阻尼动态拟合仿真工具“ DDforge”中实现。