Journal
SCIENCE ADVANCES
Volume 6, Issue 13, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aay5999
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Funding
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [201269156 - SFB 1032]
- NIH [P41-GM104601]
- NSF [OCI-0725070, ACI-1238993, MCB-1616590, ACI-1713784]
- state of Illinois
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Macromolecules tend to respond to applied forces in many different ways. Chemistry at high shear forces can be intriguing, with relatively soft bonds becoming very stiff in specific force-loading geometries. Largely used in bionanotechnology, an important case is the streptavidin (SA)/biotin interaction. Although SA's four subunits have the same affinity, we find that the forces required to break the SA/biotin bond depend strongly on the attachment geometry. With AFM-based single-molecule force spectroscopy (SMFS), we measured unbinding forces of biotin from different SA subunits to range from 100 to more than 400 pN. Using a wide-sampling approach, we carried out hundreds of all-atom steered molecular dynamics (SMD) simulations for the entire system, including molecular linkers. Our strategy revealed the molecular mechanism that causes a fourfold difference in mechanical stability: Certain force-loading geometries induce conformational changes in SA's binding pocket lowering the energy barrier, which biotin has to overcome to escape the pocket.
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