Dynamic Graph Model Of Mabs N-Linked Glycosylation And Simulation Platform

Monoclonal antibody (mAb) drug is one of the most valuable types of drugs currently in the international market. The mAb drugs are obviously in short supply for the poor understanding of the mechanism of mAbs manufacture and the immatureness of the preparation batch process, although the demand of mAb drugs is exuberant. N-linked glycosylation reaction is an important part of the preparation of monoclonal antibody drugs, and is embedded in most of mAbs manufacture. The research of N-linked glycosylation reaction generally involve glycosylation reaction network and glycosylation reaction dynamic model. In this paper, we discuss the principle and method of glycosylation reaction network and dynamic model, and develop N-linked glycosylation reaction simulation platform.For generation of glycosylation reaction network, we introduce the method of graph theory, and use graph model to describe N-linked glycoform and N-linked glycosylation reaction network. Based on the description, N-linked glycosylation reaction conditions can be represented by glycosylation reaction rules table. With the branch and bound method, the glycosylation reaction network can be generated by reaction rules table.For the dynamic model of glycosylation reaction, we point out that the N-linked glycosylation reaction dynamic model contains two parts, one is a glycoprotein transfer process, and the second is N-linked glycosylation reaction process. Glycoprotein transfer process describe how the protein manufactured transfer in Golgi, and N-linked glycosylation reaction process is described how to connect to oligosaccharide in the protein. We can deduce the glycosylation reaction dynamic equation from the two parts, and can calculate corresponding dynamic process.For N-linked glycosylation reaction simulation, we develop N-linked glycosylation reaction simulation platform GMV. In GMV, users can set up all kinds of model parameters by the graphical interface, and can observe the change of each glycoform content by glycosylation reaction dynamic process monitoring window, and reaction parameters can be adjusted automatically by the genetic algorithm module that makes the simulation result is consistent with the experimental result.