This Article Full Text Full Text (PDF) All Versions of this Article: biophysj.106.086116v1 93/2/442    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kony, D. B. Articles by Hünenberger, P. H. Search for Related Content PubMed PubMed Citation Articles by Kony, D. B. Articles by Hünenberger, P. H.

Explicit-Solvent Molecular Dynamics Simulations of the Polysaccharide Schizophyllan in Water

David B. Kony ^*, Wolfgang Damm , Serge Stoll , Wilfred F. van Gunsteren ^* and Philippe H. Hünenberger ^*

^* Laboratory of Physical Chemistry, ETH Zürich, CH-8093 Zürich, Switzerland; Schrodinger, New York, New York 10036; and CABE, Department of Inorganic, Analytical and Applied Chemistry, Science II, University of Geneva, CH-1211 Geneva 4, Switzerland

Correspondence: Address reprint requests to David Kony, Tel.: 41-1-632-5503; Fax: 41-1-632-1039; E-mail: david{at}igc.phys.chem.ethz.ch.

Schizophyllan is a ß(13)-D-glucan polysaccharide with ß(16)-branched lateral glucose residues that presents a very stiff triple-helical structure under most experimental conditions. Despite the remarkable stability of this structure (which persists up to 120°C in aqueous solution), schizophyllan undergoes a major change of state around 7°C in water that has been hypothesized to result from an order-disorder transition in the lateral residues. This hypothesis is only supported by indirect experimental evidence and detailed knowledge (at the atomic level) concerning hydrogen-bonding networks, interactions with the solvent molecules, orientational freedom of the lateral residues, and orientational correlations among them is still lacking. In this study explicit-solvent molecular dynamics simulations of a schizophyllan fragment (complemented by simulations of its tetrasaccharide monomer) are performed at three different temperatures (273 K, 350 K, and 450 K) and with two different types of boundary conditions (finite nonperiodic or infinite periodic fragment) as an attempt to provide detailed structural and dynamical information about the triple-helical conformation in solution and the mechanism of the low-temperature transition. These simulations suggest that three important driving forces for the high stability of the triple helix are i), the limited conformational work involved in its formation; ii), the formation of a dense hydrogen-bonding network at its center; and iii), the formation of interchain hydrogen bonds between main-chain and lateral glucose residues. However, these simulations evidence a moderate and continuous variation of the simulated observables upon increasing the temperature, rather than a sharp transition between the two lowest temperatures (that could be associated with the state transition). Although water-mediated hydrogen-bonded association of neighboring lateral residues is observed, this interaction is not strong enough to promote the formation of an ordered state (correlated motions of the lateral residues), even at the lowest temperature considered.