Molecular dynamics simulations of biotin in aqueous solution

Molecular dynamics simulations have been used to study the conformational properties and dynamics of biotin in explicit water for the first time. Three simulations, started from different initial conformations, generate similar results, which are characterized in terms of intramolecular distance, radius of gyration, root-mean-square deviation of all atom coordinates, and solvent-accessible surface area. The simulations indicate that biotin in aqueous solution is highly flexible and jumps between extended, semifolded, and folded states. The folded conformations via intramolecular hydrogen bonding are observed. Interestingly, many semifolded biotin molecules involving water-mediated hydrogen bonds between the ureido group and the carboxyl group of the side chain are also observed. The folded and semifolded states of biotin are likely to cause the hydrogen bonding cooperativity, which will activate the 1-NH protons and facilitate the electrophilic substitution of the 1-NH. The flexibility of biotin, the water molecules, and the hydrogen bonding cooperativity may play an essential role in activation of the 1-NH site.