Structure-conditioned amino-acid couplings: How contact geometry affects pairwise sequence preferences.
Structure-conditioned amino-acid couplings: How contact geometry affects pairwise sequence preferences.
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DOI：
10.1002/pro.4280
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Grigoryan G
中科院分区：
文献类型：
--
作者：
Holland J;Grigoryan G
将蛋白质的序列与其构象联系起来是结构预测和序列设计的核心挑战。统计接触势及其解释侧链方向和其他几何描述符的更具描述性的版本，已成为表示序列结构关系中二阶贡献的简单但有用的方法。在这里，我们问当成对势以相互作用的主链片段的完全定义的几何形状为条件时会发生什么。我们表明，由此产生的结构条件耦合能量更准确地反映了作为结构背景函数的配对偏好。这些结构调节的能量更可靠地编码天然序列信息，并且与实验确定的耦合能更高度相关。按结构对相互作用主题的数据库进行聚类会产生相似能量的集合，并且按能量对它们进行聚类会产生相似结构的集合。通过比较多对相互作用基序并显示结构相似性和能量相似性密切相关，我们提供了模块化序列和结构元素之间的切实联系。该链接适用于结构建模，并且我们表明，与使用接触电势对相同模型进行评分相比，使用结构化条件能量对 CASP 模型进行评分与结构质量的相关性要高得多。我们得出的结论是，结构条件耦合能是模拟相互作用几何对二阶序列偏好影响的好方法。
Relating a protein's sequence to its conformation is a central challenge for both structure prediction and sequence design. Statistical contact potentials, as well as their more descriptive versions that account for side‐chain orientation and other geometric descriptors, have served as simplistic but useful means of representing second‐order contributions in sequence–structure relationships. Here we ask what happens when a pairwise potential is conditioned on the fully defined geometry of interacting backbones fragments. We show that the resulting structure‐conditioned coupling energies more accurately reflect pair preferences as a function of structural contexts. These structure‐conditioned energies more reliably encode native sequence information and more highly correlate with experimentally determined coupling energies. Clustering a database of interaction motifs by structure results in ensembles of similar energies and clustering them by energy results in ensembles of similar structures. By comparing many pairs of interaction motifs and showing that structural similarity and energetic similarity go hand‐in‐hand, we provide a tangible link between modular sequence and structure elements. This link is applicable to structural modeling, and we show that scoring CASP models with structured‐conditioned energies results in substantially higher correlation with structural quality than scoring the same models with a contact potential. We conclude that structure‐conditioned coupling energies are a good way to model the impact of interaction geometry on second‐order sequence preferences.
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