CREB-binding protein (CBP) is a multi-subunit scaffold protein complex in transcription regulation process, binding and interacting with ligands such as mixed-lineage leukemia (MLL) and c-Myb allosterically. Here in this study, we have revisited the concept of allostery in CBP via residue-based interaction energy calculation based on molecular dynamics (MD) simulations. To this end, we conducted MD simulations of KIX:MLL:c-Myb ternary complex, its binary components and kinase-inducible domain (KID) interacting domain (KIX) backbone. Interaction energy profiles and cross correlation analysis were performed and the results indicated that KIX:MLL and KIX:c-Myb:MLL complexes demonstrate significant similarities according to both analysis methods. Two regions in the KIX backbone were apparent from the interaction energy and cross correlation maps that hold a key to allostery phenomena observed in CBP. While one of these regions are related to the ligand binding residues, the other comprises of L12-G2 loop and α3 helix regions that have been found to have a significant role in allosteric signal propagation. All in all, residue-based interaction energy calculation method is demonstrated to be a valuable calculation technique for the detection of allosteric signal propagation and ligand interaction regions.

中文翻译：

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使用基于残基的相互作用能重新审视 CREB ​​结合蛋白 (CBP) 的变构。

CREB ​​结合蛋白 (CBP) 是转录调控过程中的多亚基支架蛋白复合物，与混合谱系白血病 (MLL) 和 c-Myb 等配体发生变构结合和相互作用。在本研究中，我们通过基于分子动力学 (MD) 模拟的基于残基的相互作用能计算重新审视了 CBP 中的变构概念。为此，我们对 KIX:MLL:c-Myb 三元复合物、其二元组分和激酶诱导域 (KID) 相互作用域 (KIX) 主干进行了 MD 模拟。进行了相互作用能谱和互相关分析，结果表明 KIX:MLL 和 KIX:c-Myb:MLL 复合物根据两种分析方法表现出显着的相似性。从相互作用能量和互相关图中可以看出 KIX 主干中的两个区域是 CBP 中观察到的变构现象的关键。虽然这些区域之一与配体结合残基有关，但另一个区域由 L12-G2 环和 α3 螺旋区域组成，已发现它们在变构信号传播中具有重要作用。总而言之，基于残基的相互作用能计算方法被证明是一种用于检测变构信号传播和配体相互作用区域的有价值的计算技术。