Conformational and dynamical properties of disaccharides in water: a molecular dynamics study

¹ ETH-Zürich

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

Submitted on January 17, 2006
Revised on February 24, 2006
Accepted on 15 March 2006

	Abstract

Explicit-solvent molecular dynamics simulations (50 ns, 300 K) of the eight reducing glucose disaccharides (kojibiose, sophorose, nigerose, laminarabiose, maltose, cellobiose, isomaltose and gentiobiose) have been carried out, using the GROMOS 45A4 force field (including a recently reoptimized carbohydrate parameter set), in order to investigate and compare their conformational preferences, intramolecular hydrogen-bonding patterns, torsional dynamics and configurational entropies. The calculated average values of the glycosidic torsional angles agree well with available experimental data, providing validation for the force field and simulation methodology employed in this study. These simulations show in particular that: (i) (16)-linked disaccharides are characterized by an increased flexibility, the absence of any persistent intramolecular hydrogen bond and a significantly higher configurational entropy (compared to the other disaccharides); (ii) cellobiose presents a highly persistent inter-residue hydrogen bond and a significantly lower configurational entropy (compared the other disaccharides); (iii) persistent hydrogen bonds are observed for all disaccharides (except (16)-linked)and typically involve a hydrogen donor in the reducing residue and an acceptor in the non-reducing one; (iv) the probability distributions associated with the glycosidic dihedral angles and are essentially unimodal for all disaccharides, and full rotation around these angles occurs at most once or twice for (never for & phis] ) on the 50 ns timescale; (v) the timescales associated with torsional transitions (except around and ) range from about 30 ps (rotation of hydroxyl groups) to the ns range (rotation of the lactol and hydroxymethyl groups, and around the glycosidic dihedral angle in (16)-linked disaccharides).

Key Words: GROMOS force field, configurational entropy, disaccharides conformation, hydrogen bonds, molecular dynamics, torsional dynamics