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

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), 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: 1) (1-->6)-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); 2) cellobiose presents a highly persistent interresidue hydrogen bond and a significantly lower configurational entropy (compared to the other disaccharides); 3) persistent hydrogen bonds are observed for all disaccharides (except (1-->6)-linked) and typically involve a hydrogen donor in the reducing residue and an acceptor in the nonreducing one; 4) the probability distributions associated with the glycosidic dihedral angles and psi are essentially unimodal for all disaccharides, and full rotation around these angles occurs at most once or twice for (never for psi) on the 50-ns timescale; and 5) the timescales associated with torsional transitions (except around and psi) range from approximately 30 ps (rotation of hydroxyl groups) to the nanosecond range (rotation of the lactol and hydroxymethyl groups, and around the omega-glycosidic dihedral angle in (1-->6)-linked disaccharides).

[1]  J. Brady,et al.  The role of hydrogen bonding in carbohydrates: molecular dynamics simulations of maltose in aqueous solution , 1993 .

[2]  L. Poppe.  Modeling carbohydrate conformations from NMR data : maximum entropy rotameric distribution about the C5-C6 bond in gentiobiose , 1993 .

[3]  Norman L. Allinger,et al.  A molecular mechanics force field (MM3) for alcohols and ethers , 1990 .

[4]  R. Hockney.  The potential calculation and some applications , 1970 .

[5]  Wilfred F. van Gunsteren,et al.  A generalized reaction field method for molecular dynamics simulations , 1995 .

[6]  A. French,et al.  Conformational analysis of the anomeric forms of sophorose, laminarabiose, and cellobiose using MM3. , 1992, Carbohydrate research.

[7]  J. Vliegenthart,et al.  A 1H-NMR and MD study of intramolecular hydrogen bonds in methyl β-cellobioside , 1992 .

[8]  Rengaswami Chandrasekaran,et al.  Conformation of Carbohydrates , 1998 .

[9]  Norman L. Allinger,et al.  Molecular mechanics. The MM3 force field for hydrocarbons. 1 , 1989 .

[10]  G. Ciccotti,et al.  Numerical Integration of the Cartesian Equations of Motion of a System with Constraints: Molecular Dynamics of n-Alkanes , 1977 .

[11]  M. L. Sanz,et al.  Gas chromatographic-mass spectrometric method for the qualitative and quantitative determination of disaccharides and trisaccharides in honey. , 2004, Journal of chromatography. A.

[12]  R. D. Gilbert,et al.  Cellulose structure : A review , 2000 .

[13]  I. André,et al.  NMR AND MOLECULAR MODELLING OF SOPHOROSE AND SOPHOROTRIOSE IN SOLUTION , 1995 .

[14]  B. J. Hardy,et al.  Molecular dynamics simulation of cellobiose in water , 1993, J. Comput. Chem..

[15]  K. Gardner,et al.  The structure of native cellulose , 1974 .

[16]  Christopher J. Cramer,et al.  HF/6-31G* energy surfaces for disaccharide analogs , 2001, J. Comput. Chem..

[17]  Norman L. Allinger,et al.  Molecular mechanics. The MM3 force field for hydrocarbons. 3. The van der Waals' potentials and crystal data for aliphatic and aromatic hydrocarbons , 1989 .

[18]  Alexander S. Shashkov,et al.  Nuclear overhauser effect and conformational states of cellobiose in aqueous solution , 1985 .

[19]  M. Karplus,et al.  Method for estimating the configurational entropy of macromolecules , 1981 .

[20]  A. Striegel.  Anomeric configuration, glycosidic linkage, and the solution conformational entropy of O-linked disaccharides. , 2003, Journal of the American Chemical Society.

[21]  A. Mclachlan.  Gene duplications in the structural evolution of chymotrypsin. , 1979, Journal of molecular biology.

[22]  J. L. Willett,et al.  A DFT/ab initio study of hydrogen bonding and conformational preference in model cellobiose analogs using B3LYP/6-311++G**. , 2002, Carbohydrate Research.

[23]  Alan E. Mark,et al.  The GROMOS96 Manual and User Guide , 1996 .

[24]  Myco Umemura,et al.  Structure of water molecules in aqueous maltose and cellobiose solutions using molecular dynamics simulation. II. Dynamics , 2003 .

[25]  A. Cerezo,et al.  Depicting the mm3 potential energy surfaces of trisaccharides by single contour maps: application to β-cellotriose and α-maltotriose , 2003 .

[26]  Kevin J. Naidoo,et al.  Molecular Dynamics and NMR Study of the α(1→4) and α(1→6) Glycosidic Linkages: Maltose and Isomaltose , 2001 .

[27]  Carlos A. Stortz,et al.  mm3 Potential energy surfaces of the 2-linked glucosyl trisaccharides α-kojitriose and β-sophorotriose , 2003 .

[28]  A. Shashkov,et al.  Nuclear overhauser effects for methyl β-maltoside and the conformational states of maltose in aqueous solution , 1986 .

[29]  H. Berendsen,et al.  Molecular dynamics with coupling to an external bath , 1984 .

[30]  J. Blackwell,et al.  Determination of the structure of cellulose II. , 1976, Macromolecules.

[31]  Roberto D Lins,et al.  Interaction of the disaccharide trehalose with a phospholipid bilayer: a molecular dynamics study. , 2004, Biophysical journal.

[32]  B. J. Hardy,et al.  Conformational analysis and molecular dynamics simulation of cellobiose and larger cellooligomers , 1993, J. Comput. Chem..

[33]  G. P. Johnson,et al.  B3LYP/6-31G∗, RHF/6-31G∗ and MM3 heats of formation of disaccharide analogs , 2000 .

[34]  A. French,et al.  Conformational analysis of the anomeric forms of kojibiose, nigerose, and maltose using MM3. , 1992, Carbohydrate research.

[35]  A. Shashkov,et al.  The nuclear overhauser effect and structural factors determining the conformations of disaccharide glycosides , 1988 .

[36]  Serge Stoll,et al.  Explicit-Solvent Molecular Dynamics Simulations of the β(1→3)- and β(1→6)-Linked Disaccharides β-Laminarabiose and β-Gentiobiose in Water , 2004 .

[37]  H. Berendsen,et al.  COMPUTER-SIMULATION OF MOLECULAR-DYNAMICS - METHODOLOGY, APPLICATIONS, AND PERSPECTIVES IN CHEMISTRY , 1990 .

[38]  Wilfred F. van Gunsteren,et al.  Absolute entropies from molecular dynamics simulation trajectories , 2000 .

[39]  Roberto D. Lins,et al.  A new GROMOS force field for hexopyranose‐based carbohydrates , 2005, J. Comput. Chem..

[40]  B. Meyer,et al.  Molecular dynamics simulations of maltose in water , 1996 .

[41]  Ronald M. Levy,et al.  Motions of an α‐helical polypeptide: Comparison of molecular and harmonic dynamics , 1990 .

[42]  A. French,et al.  Relaxed‐residue conformational mapping of the three linkage bonds of isomaltose and gentiobiose with MM3(92) , 1994, Biopolymers.

[43]  J. Jiménez-Barbero,et al.  Chemical Biology of the Sugar Code , 2004, Chembiochem : a European journal of chemical biology.

[44]  J. Brady,et al.  Conformational analysis and molecular dynamics simulations of maltose , 1988, Biopolymers.

[45]  Wilfred F van Gunsteren,et al.  Effect of methylation on the stability and solvation free energy of amylose and cellulose fragments: a molecular dynamics study. , 2004, Carbohydrate research.

[46]  M. Karplus,et al.  Anisotropy and anharmonicity of atomic fluctuations in proteins: Analysis of a molecular dynamics simulation , 1987, Proteins.

[47]  Paramita Dasgupta,et al.  NMR and modelling studies of disaccharide conformation. , 2003, Carbohydrate research.

[48]  J. Lehmann.  Carbohydrates: Structure and Biology , 1997 .

[49]  A. Cerezo,et al.  POTENTIAL ENERGY SURFACES OF α-(1→3)-LINKED DISACCHARIDES CALCULATED WITH THE MM3 FORCE-FIELD , 2002 .