| Malignant tumors have become one of the major diseases that threaten human life and health.Existing studies have confirmed that human plasminogen Kringle 5 induces apoptosis and inhibits tumor growth by interacting with the voltage-dependent anion channel protein VDAC1.However,the specific interaction between the two remains unclear.In this regard,the interaction mechanism between human plasminogen Kringle 5and VDAC1 was studied using molecular dynamics simulation and experimental methods.Molecular dynamics simulation was used to obtain the trajectory of the interaction between the two.The amino acid analysis of the two interacted with each other revealed that the two interacted with each other via hydrogen bonds,electrostatic forces,and van der Waals forces.The conformational aspects were investigated and It was found that the disappearance of?-sheets composed of 268 VAL,269ASN,270 ALA and 165 THR,166GLN,and 167 SER in the composite changed to random curling.The random curl consisting of 162 SER,163 ARG,164 VAL and 327 PRO,328 GLU,329 THR becomes a small beta sheet,.And 163 ARG,166 GLN interacts with 361 TYR and 357 PRO in Kringle5 through hydrogen bonding,respectively.The combined energy was analyzed and decomposed,and it was found that the combination of the two can be performed spontaneously.And electrostatic force is the main driving force for the interaction between the two.29 GLU is the key amino acid for the interaction between the two.Mutation studies were performed on key amino acids.From the reverse side,it is verified that there is an interaction between the two.Experiments were conducted using frontal chromatography and surface plasmon resonance.The results show that Kringle 5 can interact with VDAC1.In frontal chromatography,the binding constants were calculated using two methods,which were3.63×10~6L/mol and 3.5×10~6L/mol,respectively.The binding constant obtained by SPR method is 1.63×10~4 L/mol.These parameters verify the interaction between VDAC1 and Kringle 5. |
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