Zhang Haiyang, Lv Yongqin, Tan Tianwei, van der Spoel David
Beijing Key Lab of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology , Box 53, 100029 Beijing, China.
Department of Biological Science and Engineering, School of Chemistry and Biological Engineering, University of Science and Technology Beijing , 100083 Beijing, China.
J Phys Chem B. 2016 Jan 28;120(3):477-84. doi: 10.1021/acs.jpcb.5b10437. Epub 2016 Jan 15.
Fabrication of metal-organic frameworks (MOFs) with large apertures triggers a brand-new research area for selective encapsulation of biomolecules within MOF nanopores. The underlying inclusion mechanism is yet to be clarified however. Here we report a molecular dynamics study on the mechanism of protein encapsulation in MOFs. Evaluation for the binding of amino acid side chain analogues reveals that van der Waals interaction is the main driving force for the binding and that guest size acts as a key factor predicting protein binding with MOFs. Analysis on the conformation and thermodynamic stability of the miniprotein Trp-cage encapsulated in a series of MOFs with varying pore apertures and surface chemistries indicates that protein encapsulation can be achieved via maintaining a polar/nonpolar balance in the MOF surface through tunable modification of organic linkers and Mg-O chelating moieties. Such modifications endow MOFs with a more biocompatible confinement. This work provides guidelines for selective inclusion of biomolecules within MOFs and facilitates MOF functions as a new class of host materials and molecular chaperones.
制备具有大孔径的金属有机框架（MOF）引发了一个全新的研究领域，即选择性地将生物分子封装在MOF纳米孔内。然而，其潜在的包封机制尚待阐明。在此，我们报告一项关于蛋白质在MOF中封装机制的分子动力学研究。对氨基酸侧链类似物结合的评估表明，范德华相互作用是结合的主要驱动力，客体大小是预测蛋白质与MOF结合的关键因素。对封装在一系列具有不同孔径和表面化学性质的MOF中的小蛋白Trp-cage的构象和热力学稳定性分析表明，通过对有机连接体和Mg-O螯合部分进行可调修饰，在MOF表面维持极性/非极性平衡，可以实现蛋白质封装。这种修饰赋予MOF更具生物相容性的限制环境。这项工作为在MOF中选择性包封生物分子提供了指导方针，并促进MOF作为一类新型主体材料和分子伴侣发挥功能。
