Paper Info
Title
Selenoglycosides in silico: ab initio-derived reparameterization of MM4, conformational analysis using histo-blood group ABH antigens and lectin docking as indication for potential of bioactivity.
Abstract
The identification of glycan epitopes such as the histo-blood group ABH determinants as docking sites for bacterial/viral infections and signals in growth regulation fuels the interest to develop non-hydrolysable mimetics for therapeutic applications. Inevitably, the required substitution of the linkage oxygen atom will alter the derivative’s topology. Our study addresses the question of the impact of substitution of oxygen by selenium. In order to characterize spatial parameters and flexibility of selenoglycosides, we first performed ab initio calculations on model compounds to refine the MM4 force field. The following application of the resulting MM4R version appears to reduce the difference to ab initio data when compared to using the MM4 estimator. Systematic conformational searches on the derivatives of histo-blood group ABH antigens revealed increased flexibility with acquisition of additional low-energy conformer(s), akin to the behavior of S-glycosides. Docking analysis using the Glide program for eight test cases indicated potential for bioactivity, giving further experimental investigation a clear direction to testing Se-glycosides as lectin ligands.
Year
DOI
Venue
2010
10.1007/s10822-010-9392-y
Journal of computer-aided molecular design
Keywords
Field
DocType
Blood group antigens,Drug design,Lectins,Molecular mechanics,Selenoglycoside
Molecular mechanics,Ab initio quantum chemistry methods,Conformational isomerism,Docking (dog),Ligand,Computational chemistry,Chemistry,Stereochemistry,Ab initio,Glycan,In silico
Journal
Volume
Issue
ISSN
24
12
1573-4951
Citations 
PageRank 
References 
0
0.34
7
Authors
5
Name
Order
Citations
PageRank
Francesco Strino121.79
Jenn-Huei Lii212725.25
Chaitanya A. K. Koppisetty321.41
Per-Georg Nyholm441.84
Hans-Joachim Gabius531.13