Steered molecular dynamics simulations are combined with analytic theory in order to gain insights into the properties of the @entity8729 / @entity4619 catch-slip bond at the atomistic level of detail. The simulations allow us to monitor the conformational changes in the @entity8729 / @entity4619 complex in response to an external force, while the theory provides a unified framework bridging the simulation data with experiment over 9 orders of magnitude. The theory predicts that the probability of bond dissociation by the catch mechanism is extremely low in the simulations; however, a few or even a single trajectory can be sufficient for characterization of the slip mechanism. Theoretical analysis of the simulation data shows that the bond responds to the force in a highly nonlinear way, with the bond @entity2693 changing considerably as a function of the force ramp rate. The Langevin description of the simulation provides spring constants of the proteins and the binding interaction and gives the friction coefficient associated with the receptor-ligand motion in water. The estimated relaxation time shows that the simple probabilistic description is accurate for the experimental regime and remains approximately valid for the high ramp rates used in simulations. The simulations establish that bond deformation occurs primarily within the @entity8729 receptor region. The two interaction sites within the binding pocket dissociate sequentially, raising the possibility of observing these independent @entity397 events in experiment. The stronger interaction that determines the overall properties of the bond dissociates first, indicating that the experimental data indeed capture the main @entity397 event and not the secondary weaker site @entity397 . The main @entity397 event involves the interaction between the @entity460 ion of the receptor and the ligand residue FUC-623. It is followed by new interactions, supporting the sliding-rebinding behavior observed in the earlier simulation [ Lou, J. Zhu, C. Biophys. J. 2007 , 92 , 1471 - 1485 ]. The weaker binding site shows fewer interaction features, suggesting that the sliding-rebinding behavior may be determined by the unique properties of the @entity460 site. The agreement between simulation and experiment provided by the two-pathway and deformation models, each containing only four parameters, indicates that the essential physics of the catch-slip bond should be relatively simple and robust over a wide range of pulling regimes.

Atomistic simulation combined with analytic theory to study the response of the XXXX / @entity4619 complex to an external force.

@entity4619 :: ('6404', 'Gene') :: ['PSGL-1'] @entity397 :: ('MESH:D012421', 'Disease') :: ['rupture'] @entity8729 :: ('6403', 'Gene') :: ['P-selectin'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity2693 :: ('MESH:C566112', 'Disease') :: ['stiffness']
@entity8729 :: (6403,Gene) :: ['P-selectin']
