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Int. J. Mol. Sci. 2007, 8(1), 13-28; doi:10.3390/i8010013

Understanding the Selectivity Mechanism of the Human Asialoglycoprotein Receptor (ASGP-R) toward Gal- and Man- type Ligands for Predicting Interactions with Exogenous Sugars

1
Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via Risorgimento 35, 56126 Pisa, Italy
2
Dipartimento di Scienze Farmaceutiche, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy
*
Author to whom correspondence should be addressed.
Received: 2 August 2006 / Revised: 10 November 2006 / Accepted: 14 December 2006 / Published: 29 January 2007
(This article belongs to the Special Issue Virtual Combinatorial Synthesis and Drug Design)
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Abstract

A practical approach for addressing the computer simulation of protein-carbohydrate interactions is described here. An articulated computational protocol was setup and validated by checking its ability to predict experimental data, available in theliterature, and concerning the selectivity shown by the Carbohydrate Recognition Domain(CRD) of the human asialoglycoprotein receptor (ASGP-R) toward Gal-type ligands. Somerequired features responsible for the interactions were identified. Subsequently the sameprotocol was applied to monomer sugar molecules that constitute the building blocks foralginates and ulvans. Such sugar polymers may supply a low-cost source of rare sugars witha potential impact on several industrial applications, from pharmaceutical to fine chemicalindustry. An example of their applicative exploitation could be given by their use indeveloping biomaterial with adhesion properties toward hepatocytes, through interactionwith the ASGP-R. Such a receptor has been already proposed as a target for exogenousmolecules, specifically in the case of hepatocytes, for diagnostic and therapeutic purposes.The DOCK5.2 program was used to search optimal locations of the above ligands of interestinto CRD binding site and to roughly estimate interaction energies. Finally, the binding ∆G oftheoretical protein-ligand complexes was estimated by using the DelPhi program in which thesolvation free energy is accounted for with a continuum solvent model, by solving the Poisson-Boltzmann equation. The structure analysis of the obtained complexes and their ∆G values suggest that one of the sugar monomers of interest shows the desired characteristics.
Keywords: human asialoglycoprotein receptor; molecular docking; DelPhi; natural sugar polymers. human asialoglycoprotein receptor; molecular docking; DelPhi; natural sugar polymers.
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Massarelli, I.; Murgia, L.; Bianucci, A.M.; Chiellini, F.; Chiellini, E. Understanding the Selectivity Mechanism of the Human Asialoglycoprotein Receptor (ASGP-R) toward Gal- and Man- type Ligands for Predicting Interactions with Exogenous Sugars. Int. J. Mol. Sci. 2007, 8, 13-28.

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