Structural flexibility of hyaluronan oligomers as probed by molecular modelling
A. Tafi, F. Manetti, F. Corelli, S. Alcaro, and M. Botta
1Dipartimento Farmaco Chimico Tecnologico, Università
degli Studi di Siena, Via Aldo Moro, I-53100 Siena, Italy; 2Dipartimento
di Scienze Farmacobiologiche, Università di Catanzaro “Magna
Græcia”, Complesso Ninì Barbieri, I-88021 Roccelletta
di Borgia (CZ), Italy
Abstract: In the last few years, molecular modeling
studies have been published that are devoted to a better understanding
of the structural flexibility of hyaluronan (HA). Further conformational
investigations, however, are needed on this polysaccharide, such as
the application of statistical methods to perform enhanced one-step
conformational analyses of its subunits. Moreover, the adjustment of
assisted model building and energy refinement (AMBER) force field could
provide the appropriate computational tool to study the interactions
of HA and its derivatives with proteins. The present paper reports a
combined Monte Carlo (MC) and molecular dynamics (MD) approach applied
to the conformational study of HA, using an adjusted version of AMBER
force field and the generalized Born solvent-accessible surface area
(GB/SA) continuum solvation model. The MC approach turned out to be
extremely effective to outline a conformational survey of the disaccharides
constituting HA. Complete sets of conformations of the monomers were
provided for the first time, some of which had never been predicted.
MD technique, integrating the MC results, correctly reproduced the unusual
stiffness of HA and predicted the existence of a minor skew-boat conformation
of the b-D-glucuronic
moiety. The computational approach, as a whole, improved the comprehension
of the dynamic behavior of HA and offered a clear causal explanation
of the relative dynamics of the glycosidic linkages.
*Pure Appl.Chem. 75,
141�419 (2003). An issue of reviews and research papers based on
lectures presented at the 23rd IUPAC International Symposium on the
Chemistry of Natural Products, Florence, Italy, 28 July � 2 August 2002.
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