论文标题
与疏水模型口袋结合的各向异性配体的亲和力，动力学和途径
Affinity, Kinetics, and Pathways of Anisotropic Ligands Binding to Hydrophobic Model Pockets
论文作者
论文摘要
使用通用口袋配体模型的显式水分子动力学（MD）模拟，我们研究了小配体的化学和塑造各向异性如何影响其与疏水结合位点相关的亲和力，动力学速率和途径。特别是，我们研究了所有相似的分子大小的芳族化合物，但由各种亲水或疏水残基有所不同。我们证明，最疏水的切片通常主要是在与腔与腔结合结合后的脱叶，这表明不同化学单元的特定水合可以通过“疏水扭矩”来指导方向途径。此外，我们发现与以前因转化波动引起的球形配体观察到的动力学屏障相比，具有双峰定向波动的配体具有显着增加的结合障碍。我们说明了这些动力学障碍物是配体特异性的，它们会影响结合时间和未连接时间，我们观察到我们研究的配体之间存在很大的差异。
Using explicit-water molecular dynamics (MD) simulations of a generic pocket-ligand model we investigate how chemical and shape anisotropy of small ligands influences the affinities, kinetic rates and pathways for their association to hydrophobic binding sites. In particular, we investigate aromatic compounds, all of similar molecular size, but distinct by various hydrophilic or hydrophobic residues. We demonstrate that the most hydrophobic sections are in general desolvated primarily upon binding to the cavity, suggesting that specific hydration of the different chemical units can steer the orientation pathways via a `hydrophobic torque'. Moreover, we find that ligands with bimodal orientation fluctuations have significantly increased kinetic barriers for binding compared to the kinetic barriers previously observed for spherical ligands due to translational fluctuations. We exemplify that these kinetic barriers, which are ligand specific, impact both binding and unbinding times for which we observe considerable differences between our studied ligands.
