探究蛋白质折叠与结合稳定性背后的侧链结构组织
Investigating the side-chain structural organization behind the stability of protein folding and binding
AI总结：
本研究通过分析蛋白质数据集的氨基酸组成与残基间相互作用能网络，发现远程库仑相互作用决定热稳定性，而分子间范德华能量与结合亲和力相关。
摘要：
决定蛋白质-蛋白质结合稳定性的分子机制是什么，以及这些机制是否与决定蛋白质折叠稳定性的机制相关，目前仍很大程度上是悬而未决的问题。事实上，尽管过去付出了许多努力，我们仍然缺乏明确的模型来解释诸如蛋白质熔化温度或复合物结合亲和力等实验量。在此，我们在已知熔化温度的蛋白质数据集以及具有可靠实验结合亲和力的大型蛋白质-蛋白质复合物数据集上，研究并比较了其化学和物理特征。具体而言，我们探究了氨基酸组成以及残基间分子内和分子间相互作用能网络的组织结构。我们发现，蛋白质表面的疏水残基优先位于结合区域，而带电残基则表现出相反的行为。此外，如丝氨酸和脯氨酸等极性氨基酸的丰度与复合物的结合亲和力相关。通过分析相互作用能，我们发现远程库仑相互作用决定了热稳定性，而总的分子间范德华能量则与蛋白质-蛋白质结合亲和力相关。
英文摘要：
What are the molecular mechanisms that dictate protein-protein binding stability and whether those are related to the ones behind protein fold stability are still largely open questions. Indeed, despite many past efforts, we still lack definitive models to account for experimental quantities like protein melting temperature or complex binding affinity. Here, we investigate and compare chemical and physical features on a dataset of protein with known melting temperature as well as a large dataset of protein-protein complexes with reliable experimental binding affinity. In particular, we probed the aminoacid composition and the organization of the network of intramolecular and intermolecular interaction energies among residues. We found that hydrophobic residues present on the protein surfaces are preferentially located in the binding regions, while charged residues behave oppositely. In addition, the abundance of polar amino acid like Serine and Proline correlates with the binding affinity of the complexes. Analysing the interaction energies we found that distant Coulombic interactions are responsible for thermal stability while the total inter-molecular van der Waals energy correlates with protein-protein binding affinity.
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