The force, the heat and the shear. Three weaknesses for three perturbations!

Shear unfolding chapter two. Same question: Can proteins unfold in shearing fluid flows, and to what extent? How do the tensile forces exerted by the solvent affect the protein compared to other types of external perturbations such as thermal denaturation, or directional pulling forces used in optic/magnetic tweezers or atomic force microscopy (AFM) experiments? Before the answer: conventional all-atom molecular dynamics simulations often require too much computational effort, hence, we have developed an original methodology using Lattice Boltzmann Molecular Dynamics (LBMD) and the Optimized Potential for Efficient peptide folding Prediction (OPEP) coarse-grained model to inquire the unfolding features of a small Cold Shock Protein subjected to three different perturbations: shear flow, heat shock and pulling force. Since the implicit-solvent OPEP model inherently lacks hydrodynamics, the Lattice Boltzmann framework allowed us to realistically simulate the flow interaction with the protein, while retaining good computational efficiency with respect to explicit-solvent approaches. Here the answer: The direct comparison of the unfolding mechanisms evidenced that the three perturbations act on different weaknesses of the protein, and thus lead on average to very different unfolding pathways. Funny enough, for this small globular protein shear flow acts more similarly to thermal excitation then a direct mechanical force. Our results suggest that the interpretation of experimental studies that rely on force-spectroscopy techniques to investigate natural shear-activated systems, such as the von Willebrand factor or the bacterial adhesin FimH, is not straightforward. The paper is out here.