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Furanosides have been subjected to extensive studies owing to their inherent flexibility, which is believed to play an important role in the survival and pathogenicity of different disease-causing organisms in the human body. This study reports the binding free energy (ΔG) and specificity of arabinofuranose oligosaccharides to a protein, arabinanase (Arb43A), with the use of potential of mean force (PMF) calculations using the umbrellasampling simulations. Long molecular dynamics simulations have been carried out to understand intermolecular interactions in the arabinofuranose−protein complex. The PMF for pulling the α-(1 → 5)-linked L-arabinohexaose (ligand) from the protein provides a large free energy of binding, −16.8 kcal/mol. The ΔG of the nonreducing arabinotriose end is found to be −12.6 kcal/mol, while the ΔG of the reducing end is calculated to be −7.7 kcal/mol. In the absence of nonreducing arabinotrioside, the ΔG of the reducing arabinotrioside is −8.5 kcal/mol. Similarly, in the absence of reducing arabinotrioside, the ΔG of the nonreducing arabinotrioside is calculated to be −9.4 kcal/mol. The main contributing factor in the protein−arabinofuranose binding is hydrogen bonding. Acidic amino acid residues, Glu and Asp, with furanosides produce the strongest hydrogen bonding. Araf-A, B, and C construct the reducing arabinotriose, while Araf-D, E, and F construct the nonreducing arabinotriose. Since most of the hydrogen-bonding occupancies belong to Araf-D and Araf-E, the nonreducing arabinotriose is bound to protein more strongly than the reducing arabinotriose. This explains why the reducing arabinotriose can detach from the protein in nature.

Ab initio calculations were carried out to understand the reactivity and stability of some uracil derivatives, cytosine, 1-methyl cytosine, and cytidine in solvents, water, dimethyl sulfoxide (DMSO), n -octanol, and chloroform. Geometries were fully optimized at MP2 and B3LYP using the 6-31+G(d,p) basis set by applying the Solvation Model on Density (SMD) in solvent systems. The syn conformer of cytidine (cytidine II) is the most stable conformer in the gas phase, while the anticonformer (cytidine IV) is most stable in all of the solvents. Solvation free energy and polarizability values in different solvents decrease in the order water > DMSO > n -octanol > chloroform, while dipole moment, first-order hyperpolarizability, and HOMO–LUMO energy gap values follow the order of polar protic solvent (water and n -octanol) > polar aprotic solvent (DMSO) > nonpolar solvent (chloroform). The solvation free energy, dipole moment, polarizability, and first-order hyperpolarizability values also follow the order of cytosine > 1-methyl cytosine > cytidine. To illustrate that the molecular properties correlate well with the reactivity of the molecules, ab initio calculations were carried out for the reaction of uracil derivatives with Br 2 in the gas phase, water, DMSO, n -octanol, and chloroform. All ground and transition state geometries were fully optimized at B3LYP/6-31+G(d,p), and energies were also calculated at G3MP2 for cytosine and 1-methyl cytosine. For cytosine and 1-methyl cytosine, Gibbs energies of activation decrease with the polarity of the solvent that is chloroform > n -octanol > DMSO > water, while the Gibbs energies of activation for the reaction with cytidine decrease in the order of water > DMSO > n -octanol > chloroform. These results suggest that solvent polarity is very important for the stability and reactivity of uracil derivatives. Hydrogen bonding may also play an important role mainly for cytidine. Free energies of activation decrease with the size of the molecule, i.e., cytosine > 1-methyl cytosine > cytidine.