Energy minimized crystal structures of P-selectins based on molecular dynamics simulation: leading to two average structures capable of designing anti-thrombotic agents

Abstract

In the most frequent cardiovascular events, deep vein thrombosis has been one of the most prominent causes of morbidity and mortality. Soluble P-selectin plays an essential role in the formation of thrombosis and has been considered a target of anti-thrombotic agents. With regard to molecular modeling, here the theoretical studies were performed on variant P-selectin structures. By removing SLe^x from PDB 1G1R or removing both SLe^x and PSGL-1 from PDB 1G1S, minimizing the energy of the formed structures, and performing molecular dynamics simulations, two average structures of P-selectins were obtained. A series of comparisons of the properties reflecting the quality of the two average structures, such as the backbone RMSD values, RMSF values, the change of the secondary structures, the conformation flexible regions and the correlated motions demonstrated that both of the two average structures are suitable and equally important for anti-thrombotic agent design.