Article pubs.acs.org/JPCB
Atomistic Simulation of Protein Encapsulation in Metal−Organic Frameworks Haiyang Zhang,†,‡ Yongqin Lv,*,† Tianwei Tan,*,† and David van der Spoel§ †
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 § Uppsala Center for Computational Chemistry, Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, Husargatan 3, Box 596, SE-75124 Uppsala, Sweden S Supporting Information *
ABSTRACT: 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.
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INTRODUCTION Over the past decades, metal−organic frameworks (MOFs) formed by the assembly of metal ions and organic linkers have emerged as a new class of highly crystalline hybrid inorganic− organic porous materials.1 Because of the unique properties, including ultrahigh surface area and porosity, chemically tunable and uniform pore sizes and surfaces, and structural diversity, MOFs have been designed for a variety of applications such as gas storage/separation, catalysis, chemical sensing, biomedical imaging, and drug delivery.2−8 In recent years, encapsulation of biomolecules such as proteins in MOFs has evolved as a potential new application of MOF materials. This application however is restricted by the microporous regime (
