Multiple molecular dynamics simulations of human LOX‐1 and Trp150Ala mutant reveal the structural determinants causing the full deactivation of the receptor

摘要: Multiple classical molecular dynamics simulations have been applied to the human LOX-1 receptor clarify role of Trp150Ala mutation in loss binding activity. Results indicate that substitution this crucial residue, located at dimer interface, markedly disrupts wild-type dynamics. The causes an irreversible rearrangement subunits interaction pattern protein allows maintaining a specific symmetrical motion monomers. dislocation determines linearity arginines residues composing basic spine and consequent alteration long-range electrostatic attraction substrate. Moreover, anomalous arrangement observed mutated also affects integrity hydrophobic tunnel, actively involved short-range recognition combined effect these structural rearrangements generates impairing function.