Molecular Dynamics model of peptide-protein conjugation: case study of covalent complex between Sos1 peptide and N-terminal SH3 domain from Grb2.

ABSTRACT: We have investigated covalent conjugation of VPPPVPPRRRX' peptide (where X' denotes N^ε-chloroacetyl lysine) to N-terminal SH3 domain from adapter protein Grb2. Our experimental results confirmed that the peptide first binds to the SH3 domain noncovalently before establishing a covalent linkage through reaction of X' with the target cysteine residue C32. We have also confirmed that this reaction involves a thiolate-anion form of C32 and follows the S_N2 mechanism. For this system, we have developed a new MD-based protocol to model the formation of covalent conjugate. The simulation starts with the known coordinates of the noncovalent complex. When two reactive groups come into contact during the course of the simulation, the reaction is initiated. The reaction is modele

SUBMITTER: Luzik DA 

PROVIDER: S-EPMC6934455 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature