Explicit-solvent molecular dynamics simulations of the polysaccharide schizophyllan in water

¹ ETHZ
² Schrodinger Inc
³ University

^* To whom correspondence should be addressed. E-mail: david{at}igc.phys.chem.ethz.ch.

Submitted on March 31, 2006
Revised on May 26, 2006
Accepted on 4 January 2007

	Abstract

Schizophyllan is a (13)-D-glucan polysaccharide with (16)-branched lateral glucose residues that presents a very stiff triple-helical structure under most experimental conditions. In spite of the remarkable stability of this structure (which persists up to 120°C in water), schizophyllan undergoes a major state transition around 7°C in water, that has been hypothetized 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 the present study explicit-solvent molecular dynamics simulations of a schizophyllan fragment (complemented by simulations of its tetrasaccharide monomer) are performed at three different temperatures (273K, 350K and 450K) and with two different types of boundary conditions (finite non-periodic 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 net work at its center; (iii) the formation of inter-chain hydrogen bond 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 neighbouring 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.

Key Words: OPLS-AA-SEI force field, computer simulation, molecular dynamics, schizophyllan, state transition