In silico simulation of glycosylation and related pathways

Abstract

Glycans participate in a vast number of recognition systems in diverse organisms in health and in disease. However, glycans cannot be sequenced because there is no sequencer technology that can fully characterize them. There is no “template” for replicating glycans as there are for amino acids and nucleic acids. Instead, glycans are synthesized by a complicated orchestration of multitudes of glycosyltransferases and glycosidases. Thus glycans can vary greatly in structure, but they are not genetically reproducible and are usually isolated in minute amounts. To characterize (sequence) the glycome (defined as the glycans in a particular organism, tissue, cell, or protein), glycosylation pathway prediction using in silico methods based on glycogene expression data, and glycosylation simulations have been attempted. Since many of the mammalian glycogenes have been identified and cloned, it has become possible to predict the glycan biosynthesis pathway in these systems. By then incorporating systems biology and bioprocessing technologies to these pathway models, given the right enzymatic parameters including enzyme and substrate concentrations and kinetic reaction parameters, it is possible to predict the potentially synthesized glycans in the pathway. This review presents information on the data resources that are currently available to enable in silico simulations of glycosylation and related pathways. Then some of the software tools that have been developed in the past to simulate and analyze glycosylation pathways will be described, followed by a summary and vision for the future developments and research directions in this area. Graphical Abstract