BAR domain superfamily proteins are considered to have the universal ability to induce membrane curvature. Many coarse-grained and all-atom molecular dynamics (MD) simulation studies have explained the process of N-BAR domain sensing and inducing membrane bending in detail. They focus on simulating the binding-sensing-bending process. However, many researchers have overlooked an interesting question-what structural changes did the N-BAR domain itself produce during the entire process? What structural and mechanical properties should N-BAR dimers have in order to perform biochemical functions? With these two questions in mind, we selected the PICK1 N-BAR domain to conduct umbrella sampling dynamics simulations in two directions. We found that helix kinks on the monomer not only give curvature to the monomer, but also provide extra flexibility that is necessary to perform monomer’s biochemical functions. We noted them as key residues. There are other important key residues, some of which determine the curvature of the BAR dimer together with helix kinks, by binding BAR monomers into a dimer. Other key residues are found inside the BAR monomer, binding the three helices of the whole monomer into a whole. The results indicate that the overall structure of the N-BAR dimer is rigid. But at the same time, the key parts will also have certain flexibility, so that the BAR dimer can better complete the biological function of the curved membrane

Investigating the mechanical properties and flexibility of N-BAR domains in PICK1 by molecular dynamics simulations

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