Bringing Force Probe Molecular Dynamics Simulations Closer to Experiments

Abstract

The interaction between Streptavidin and Biotin is one of the strongest known non covalent bonds in nature. For this reason, many experimental and computational studies have been done on this complex, which revealed many details on binding and unbinding of biotin, which turned out to be an astonishingly complex process.However, taken all these studies together and despite considerable technical advances over the past years, there is still a time scale gap remaining, i.e., the loading rates possible in force spectroscopy experiments and those achievable in molecular dynamics (MD) simulations hardly overlap.Recent high speed force spectroscopy (HS-FS) experiments by Scheuring offer the possibility to reach pulling velocities up to 5 mm/s.Here we present extensive MD simulations covering pulling velocities from 0.5 mm/s to 50 m/s, thus providing an overlap of one order of magnitude with experimental time scales. Further, to resemble the AFM experiment as closely as possible in the simulations, we modeled the PEG-linker between Biotin and the cantilever as a wormlike chain and chose a spring constant of the pulling potential to match the stiffness of the cantilever in HS-FS experiments done by Scheuring.Over the whole interval, agreement of the probability distributions of unbinding forces is seen. Taken together, these data cover unbinding time scales over 10 orders of magnitude, which offers a unique opportunity to compare against several proposed transition state treatments of this process.