Molecular Structure Of P-selectin And PSGL-1 Under Blood Flow Shear

Inflammation is an important physiological process.It is the first defense of human body to against bacterial invasion.With the interatction of intergrins,selectins and chemokine receptors,leukocytes are recruited to specific sites.P-selectin of leukocytes and PSGL-1 of endothelial cells complex is the first responding complex in acute inlasmmation.Invertigating in atom level of P-selectin & PSGL-1 would gave us insights into the precesses of inlammation and thrombosis,and provide some clues for next steop pharmaceutical research.Some studys verified that P-selectin & PSGL-1 exist slide-catch-slide mechanism under force.However,an integral explanation of the catch bond mechanism still not existed.In this paper,we improve current theory and propose the an explanation of catch bond mechanism.We utilized molecular dynamics simulation(MD)to study the complex under atom level: balance MD and tensile MD under constand speed and constant force.We taked 27 comformation based on the power spectrum of 10 ns constand speed MD,which will be MD by 9 different forces under 50 ns.After studying of the trajectory,we find out three different kinds of dissociation path of complex: Binding,Stablebinding and Directlypulloff.With studying under VMD,three kinds of model are found out from Binding model.There are Binding(notbreak),Binding(break)and Binding(strength).With the trajectory analysis under Binding models,we believe that the sulfation tyrosine and glycosylation of PSGL-1 contribute to prolong the lifetime of this complex.The interface of complex rotate under force,which lead to the unbinding between glycosylation and switch3 of P-selectin.If the new hydrogen bond couples are produced between Tys5 and P-selectin when Tys10 still binding with P-selectin firmly,the lifetime of complex will be prolonged.And Tys5 have higher affinity than Tys7 or Tys10 to produce hydrogen bond,which will be verified in this paper.Moreover,if the glycosylation rebind to P-selectin and form a stable binding after rotation in this period,the lifetime of complex will be further enhance.On the other hand,glycosylation have high possibility to produce new hydregen bond with switch3 of P-selectin if the glycosylation have rotation behavior under force induced,which will also enhance the atom interaction on the complex interface.