Probabilistic identification of saccharide moieties in biomolecules and their protein complexes

Abstract

The chemical composition of saccharide complexes underlies their biomedical activities as biomarkers for cardiometabolic disease, various types of cancer, and other conditions. However, because these molecules may undergo major structural modifications, distinguishing between compounds of saccharide and non-saccharide origin becomes a challenging computational problem that hinders the aggregation of information about their bioactive moieties. We have developed an algorithm and software package called "Cheminformatics Tool for Probabilistic Identification of Carbohydrates" (CTPIC) that analyzes the covalent structure of a compound to yield a probabilistic measure for distinguishing saccharides and saccharide-derivatives from non-saccharides. CTPIC analysis of the RCSB Ligand Expo (database of small molecules found to bind proteins in the Protein Data Bank) led to a substantial increase in the number of ligands characterized as saccharides. CTPIC analysis of Protein Data Bank identified 7.7% of the proteins as saccharide-binding. CTPIC is freely available as a webservice at (http://ctpic.nmrfam.wisc.edu).

Too sweet: cheminformatics for deglycosylation in natural products

“…The validation of the SRU cannot be done otherwise than visually and with a known reference dataset, as there is not, for now, a reference algorithm that the performance can be compared to. CTPIC [ 16 ], published recently, is the only work that tackles the sugar detection problem in biological molecules. However, this probabilistic approach is designed to distinguish if a molecule is a sugar or is derived from one, from a molecule that is not.…”

“…This problem underlines that the question in theoretical deglycosylation is not whether a particular substructure is chemically a sugar but rather whether it is a redundant sugar-like structure that can obstruct the analysis of the parental structure within the molecule and can be removed without information loss. In several studies [ 13 , 15 , 16 ] and applications, such as Scaffold Hunter [ 17 , 18 ], the “terminal ring sugars” are said to be removed, and this also demands a more thorough definition of what are terminal sugars and ring sugars. The latter suggests that there are also non-terminal and linear sugar substructures in molecular constructs.…”

A perspective on the PDB’s impact on the field of glycobiology

“…Much of this has now been corrected through the use of improved deposition and remediation tools for carbohydrates ( https://www.wwPDB.org/documentation/carbohydrate-remediation ). Also, there are now software search tools that use either atom connectivity data ( 14 ) or actual structural footprints https://dev.glycam.org/portal/gf_home/ ( 15 ) to find relevant structures in the PDB. A recent application of one of these tools suggests that the percentage of depositions containing a carbohydrate moiety is actually 7.7% ( 14 ).…”

Too sweet: cheminformatics for deglycosylation in natural products

“…The validation of the SRU cannot be done otherwise than visually and with a known reference dataset, as there is not, for now, a reference algorithm that the performance can be compared to. CTPIC [16], published recently, is the only work that tackles the sugar detection problem in biological molecules.…”