Effect Of Cu(?) On The Ability Of Trypsin Scavenging Free Radicals By Molecular Dynamics Simulations By Molecular Dynamics Simulations

Trypsin is a typical protein hydrolase,consisting of two equal barrel structure domain A and domain B.The beta fold,S1 pocket,Loop1 and Loop2 are the characteristic of its structure..Previous studies have found that copper ions can influence the protein conformation,making the random curl or alpha helix structure turn into a neat beta folding or gathered into beta folded piece.Copper ions can significantly affect protein conformation in active site,making protein conformation more compact.We had proved that trypsin can scavenge free radicals with biological experiments,and the ability can be affected after adding the Cu(?).Based on the experimental results and literature accumulation that Cu(?)greatly influence on protein conformation,we use molecular dynamics method to explore the interaction of copper ion and trypsin,and to reveal the effects of copper ion on scavenging free radicals and the mechanism of this result.We built the structure of copper ion-trypsin,trypsin,inhibitors-trypsin structure to simulate by molecular dynamics simulation method.The analysis include stability of protein,SASA,hydrophobicity and the principal component analysis,especially the hydrogen bond between beta folded.The results showed that(1)copper ions can reduce the radius of gyration of trypsin,making the structure of trypsin closer;(2)copper ions can increase solvent accessible surface area in trypsin,hydrophobic interactions and the number of contact between amino acids also increased;(3)copper ions can active the S1 pocket and increase the amino acid correlation,making the conformation of trypsin compact;(4)copper ion increase the number of hydrogen bond in the beta-fold and make beta fold more neat.Amino acids 226 Gly,Ala 160,leu 135 Gln,20 Tyr,155Leu and 135 Lys in beta-fold play a key role in the formation of hydrogen-bond.To sum up,the copper ion significantly changed the conformation of trypsin and enhanced the activity of trypsin,so it can improve the ability of scavenging free radicals in trypsin.This study can provide theoretical basis for metal ions' s influence on protein conformation and antioxidant effect,also expecting for the development of a new way on scavenging free radicals.