Protein mechanical unfolding: Importance of non-native interactions.

Mechanical unfolding of the fourth domain of Distyostelium discoideum filamin (DDFLN4) was studied by all-atom molecular dynamics simulations, using the GROMOS96 force field 43a1 and the simple point charge explicit water solvent. Our study reveals an important role of non-native interactions in the unfolding process. Namely, the existence of a peak centered at the end-to-end extension ΔR∼22 nm in the force-extension curve is associated with breaking of non-native hydrogen bonds. Such a peak has been observed in experiments but not in Go models, where non-native interactions are neglected. We predict that an additional peak occurs at ΔR∼2 nm using not only GROMOS96 force field 43a1 but also Amber 94 and OPLS force fields. This result would stimulate further experimental studies on elastic properties of DDFLN4. [ABSTRACT FROM AUTHOR]