Investigating Hydrophobic Interactions During Substrate Rupture: An SMD Simulation Study

The present investigation involves multiple simulations utilizing SMD (Steered Molecular Dynamics) to ascertain the frequency of hydrophobic interactions between the substrate, which is subjected to mechanical strain or rupture force, and binding channel residues. Amber 20 was employed to carry out the pulling simulations, where the reaction coordinate was defined as the distance between the calcium ion (Ca)_D-PL(C2) atom. The pulling velocity was set to 10 Å/ns, and D-PL was pulled from approximately 15.0 to 40.0 Å on different reaction coordinates. To ensure that the pulled atoms closely adhered to the constraints, a large spring constant k (k = 100 kcal mol−1 Å −2) was utilized, and each system was subjected to a total of 5 independent simulations. The MM/GBSA (Molecular Mechanics/Generalized Born Surface Area) of each residue in each frame was calculated by decomposing CPPTRAJ, and subsequently, the frequency of non-polar solvation between binding channel residues and D-PL in each frame was tallied. Any non-zero solvation energy was deemed to generate hydrophobic interactions, and vice versa.