Lignin and phenolic compounds have been shown as the main recalcitrance for biomass decomposition, as they inhibit a number of lignocellulose-degrading enzymes. Understanding the inhibition mechanisms and energetic competitions with the native substrate is essential for the development of lignin resistive enzymes. In this study, atomistic detail of the size-dependent effects and binding modes of monomeric coniferyl alcohol, dimeric oligolignol, and tetrameric oligolignol made from coniferyl alcohols on the GH11 xylanase from Bacillus firmus strain K-1 was investigated by using molecular docking and atomistic molecular dynamics (MD) simulations. From the MD simulation results on the docked conformation of oligolignol binding within the “Cleft” and the “N-terminal,” changes were observed both for protein conformations and positional binding of ligands, as binding with “Thumb” regions was found for all oligolignin models. Moreover, the uniquely stable “N-terminal” binding of the coniferyl alcohol monomer had no effect on the highly fluctuated Thumb region, showing no sign of inhibitory effect, and was in good agreement with recent studies. However, the inhibitory effect of oligolignols was size dependent, as the estimated binding energy of the tetrameric oligolignol became stronger than that of the xylohexaose substrate, and the important binding residues were identified for future protein engineering attempts to enhance the lignin resistivity of GH11.

Size-dependent binding modes of coniferyl alcohol monomers (upper panels) and the dimers (lower panels). Uniquely stable “N-terminal” binding of the monomer is shown to have no effect on the binding pocket, and hence no sign of inhibition, which was in good agreement with some recent studies.

中文翻译：

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寡聚木酚的大小和结合方式对GH11木聚糖酶抑制作用的影响通过分子建模技术揭示。

木质素和酚类化合物已被证明是生物质分解的主要障碍，因为它们抑制了许多木质纤维素降解酶。了解抑制机制和与天然底物的能量竞争对于木质素抗性酶的发展至关重要。在这项研究中，由针叶醇制得的单体松柏醇，二聚低聚木酚和四聚低聚木酚对牢固芽孢杆菌菌株K-1的GH11木聚糖酶的尺寸依赖性效应和结合模式的原子细节通过使用分子对接和原子分子动力学（MD）模拟进行了研究。根据MD模拟结果，在“裂口”和“ N端”内寡聚寡糖结合的对接构象，观察到蛋白质构象和配体位置结合的变化，因为发现所有寡聚寡糖都与“拇指”区结合楷模。此外，松柏醇单体的独特稳定的“ N-末端”结合对高度波动的Thumb区没有影响，没有抑制作用的迹象，并且与最近的研究很好地吻合。但是，寡聚寡糖的抑制作用取决于大小，因为估计的四聚寡木酚的结合能变得比木己糖底物的结合能更强，

松柏醇单体（上图）和二聚体（下图）的尺寸依赖性结合模式。单体的唯一稳定的“ N-末端”结合被证明对结合袋没有影响，因此没有抑制迹象，这与一些最近的研究非常吻合。