Flexible regions in proteins, such as loops, cannot be represented by a single conformation. Instead, conformational ensembles are needed to provide a more global picture. In this context, identifying statistically meaningful conformations within an ensemble generated by loop sampling techniques remains an open problem. The difficulty is primarily related to the lack of structural data about these flexible regions. With the majority of structural data coming from x‐ray crystallography and ignoring plasticity, the conception and evaluation of loop scoring methods is challenging. In this work, we compare the performance of various scoring methods on a set of eight protein loops that are known to be flexible. The ability of each method to identify and select all of the known conformations is assessed, and the underlying energy landscapes are produced and projected to visualize the qualitative differences obtained when using the methods. Statistical potentials are found to provide considerable reliability despite their being designed to tradeoff accuracy for lower computational cost. On a large pool of loop models, they are capable of filtering out statistically improbable states while retaining those that resemble known (and thus likely) conformations. However, computationally expensive methods are still required for more precise assessment and structural refinement. The results also highlight the importance of employing several scaffolds for the protein, due to the high influence of small structural rearrangements in the rest of the protein over the modeled energy landscape for the loop.

中文翻译：

---

具有多种亚稳态构象的蛋白质环：采样和评分方法的挑战。

蛋白质中的柔性区域（例如环）无法用单个构象表示。取而代之的是，需要构象合奏以提供更全面的图景。在这种情况下，在循环采样技术产生的整体中识别统计上有意义的构象仍然是一个未解决的问题。困难主要与缺乏有关这些柔性区域的结构数据有关。由于大多数结构数据来自X射线晶体学，而忽略了可塑性，因此，对环刻痕方法的概念和评估提出了挑战。在这项工作中，我们在一组八个灵活的蛋白质环上比较了各种评分方法的性能。评估了每种方法识别和选择所有已知构象的能力，生成并投影潜在的能源格局，以可视化使用这些方法时获得的质量差异。尽管统计电位被设计为权衡准确性以降低计算成本，但发现统计电位可提供可观的可靠性。在大量的循环模型中，它们能够过滤出统计上不可能的状态，同时保留类似于已知（因而可能）构象的状态。但是，仍然需要计算上昂贵的方法来进行更精确的评估和结构改进。结果还突出显示了对蛋白质使用几种支架的重要性，这是由于其余蛋白质中的小结构重排对环的建模能量分布有很大的影响。