In this work we present a computational analysis together with experimental studies, focusing on the interaction between a benzothiazole (BTS) and lysozyme. Results obtained from isothermal titration calorimetry, UV-vis, and fluorescence were contrasted and complemented with molecular docking and machine learning techniques. The free energy values obtained both experimentally and theoretically showed excellent similarity. Calorimetry, UV-vis, and 3D/2D-lig-plot analysis revealed that the most relevant interactions between BTS and lysozyme are based on a predominance of aromatic, hydrophobic Van der Waals interactions, mainly aromatic edge-to-face (T-shaped) π-π stacking interactions between the benzene ring belonging to the 2-(methylthio)-benzothiazole moiety of BTS and the aromatic amino acid residue TRP108 of the lysozyme receptor. Next, conventional hydrogen bonding interactions contribute to the stability of the BTS-lysozyme coupling complex. In addition, mechanistic approaches performed using elastic network models revealed that the BTS ligand theoretically induces propagation of allosteric signals, suggesting non-physiological conformational flexing in large blocks of lysozyme affecting α-helices. Likewise, the BTS ligand interacts directly with allosteric residues, inducing perturbations in the conformational dynamics expressed as a moderate conformational softening in the α-helices H1, H2, and their corresponding β-loop in the lysozyme receptor, in contrast to the unbound state of lysozyme.

中文翻译：

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解开溶菌酶-苯并噻唑衍生物相互作用中涉及的组成和分子特征

在这项工作中，我们提出了计算分析和实验研究，重点是苯并噻唑 (BTS) 和溶菌酶之间的相互作用。从等温滴定量热法、紫外-可见光和荧光法获得的结果与分子对接和机器学习技术进行对比和补充。实验和理论上获得的自由能值显示出极好的相似性。量热法、UV-vis 和 3D/2D-lig-plot 分析表明，BTS 和溶菌酶之间最相关的相互作用是基于芳香的、疏水的范德华相互作用，主要是芳香的边对面（T 形) 属于 BTS 的 2-(甲硫基)-苯并噻唑部分的苯环与溶菌酶受体的芳香族氨基酸残基 TRP108 之间的 π-π 堆积相互作用。下一个，传统的氢键相互作用有助于 BTS-溶菌酶偶联复合物的稳定性。此外，使用弹性网络模型执行的机械方法表明，BTS 配体理论上会诱导变构信号的传播，这表明影响 α 螺旋的溶菌酶大块中的非生理构象弯曲。同样，BTS 配体直接与变构残基相互作用，引起构象动力学的扰动，表现为 α-螺旋 H1、H2 及其相应的溶菌酶受体中的 β-环中的适度构象软化，与未结合的状态相反。溶菌酶。使用弹性网络模型进行的机械方法表明，BTS 配体理论上会诱导变构信号的传播，这表明影响 α 螺旋的溶菌酶大块中的非生理构象弯曲。同样，BTS 配体直接与变构残基相互作用，引起构象动力学的扰动，表现为 α-螺旋 H1、H2 及其相应的溶菌酶受体中的 β-环中的适度构象软化，与未结合的状态相反。溶菌酶。使用弹性网络模型进行的机械方法表明，BTS 配体理论上会诱导变构信号的传播，这表明影响 α 螺旋的溶菌酶大块中的非生理构象弯曲。同样，BTS 配体直接与变构残基相互作用，引起构象动力学的扰动，表现为 α-螺旋 H1、H2 及其相应的溶菌酶受体中的 β-环中的适度构象软化，与未结合的状态相反。溶菌酶。