Molecular simulation of a single-chain antibody against AChE to explore molecular basis of inhibitory effect of 3F3 McAb on enzyme activity.
OBJECTIVE
To explore the molecular basis of the inhibitory effect of 3F3, a monoclonal antibody against acetylcholinesterase (AChE), by computer-aided molecular simulation.


METHODS
The single-chain 3F3 antibody (Sc3F3) was designed by joining VH and VL via a flexible linker (Gly4Ser)3. The amino acid sequence of the recombinant Sc3F3 was then subjected to computer-aided molecular modeling, and docking with the antigen molecule AChE to mimic the immunoactive interaction in a three-dimensional fashion.


RESULTS
The modeled structure of Sc3F3 manifested the common features of a classical antibody. Both VH and VL were composed of two ?-sheets and connecting loops. The docking profile of the action between Sc3F3 with AChE demonstrated the formation of a stable structure. The van der Waals force played an important role suggesting that the complex was formed mainly via hydrophobic interactions between Sc3F3 and AChE molecules.


CONCLUSIONS
The spatial structure of the complex of Sc3F3 and AChE showed that Sc3F3 overlaid the entrance of the active center gorge of AChE blocking the access of substrate.
Institute of Pharmacology and Toxicology, Academy of Militery Medical Sciences, Beijing 100850, China.
Chong-Zhi
CZ
Guo
Jun-Hua
JH
Wu
Yu-Xia
YX
Wang
Yuan-Dong
YD
Hu
Song
S
Li
Man-Ji
MJ
Sun
D000110:Acetylcholinesterase / Q000276:immunology* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D003198:Computer Simulation; D006825:Hybridomas / Q000166:cytology / Q000378:metabolism; D007128:Immunoglobulin Fragments / Q000737:chemistry / Q000494:pharmacology*; D008968:Molecular Conformation
D000911:Antibodies, Monoclonal; D002800:Cholinesterase Inhibitors; D007128:Immunoglobulin Fragments; D000110:Acetylcholinesterase