Natural polysaccharides are composed of basic pieces similar to a LEGO set with only a few different pieces; therefore, mainly all biological polysaccharides can be obtained with different combinations of these building blocks. Polysaccharides are compounds made up of many units of monosaccharides, dealing with a few and up to thousands of them. Glycosidic bonds that can be broken by hydrolysis link these units. These natural polymers derived from aldose or ketose via a condensation reaction.
To provide a structural base for the different biological roles that carbohydrates play, it is indispensable to be able to determine precisely the dynamic, thermodynamic and spatial properties of saccharides. This task is generally conducted using various different experimental techniques, such as X-ray, crystallography, and spectroscopy, to mention a few. This is complemented with studies made with Molecular Simulation and Computational Chemistry Modeling.
There are a few force fields that had been developed specifically for carbohydrates that take into account atomistic interactions.However, for very large molecules, such as the case of polymers,these force fields are inefficient and require long simulation times to manage such interactions. Here is where “coarse grain” models come into play, by maintaining the essence of the most relevant interactions, the model is simplified by making a “map”, with the consequent reduction in calculation time.
Our goal is to obtain a new (more compact) force field through atomistic molecular dynamics simulations, using the CHARMM36 forcefield for mono, di, and oligosaccharides, together with the iterative Boltzmann inversion (IBI) method, to be able to describe with precision the behavior of all the biological polysaccharides.
Boltzmann inversion (BI) in mostly used for bonded interaction, such as bonds, angles and torsion, it is structure-based, and for that, it only requires positions of atoms. The IBI is a natural extension of the BI method. Since the objective of the coarse-grained model is to reproduce the distribution functions of the reference system as accurately as possible, one can also iteratively refine the coarse-grained potentials using a numerical method. IBI can be used to refine both bonded and non-bonded interactions.
The first step is to obtain the atomistic simulation results. For that, we had been running simulations of several monosaccharides (pentoses and hexoses, presenting both, α and β configuration) at room pressure and temperature, using several molar concentrations.The chosen monosaccharides include several features of the configurations, such as rings of five or six atoms (furanoses and pyranoses). The nine disaccharides include the different kinds of glycoside linkage, and finally, a few oligosaccharides were also included in this set. The molecular dynamics simulations were running using the GROMACS package. From that we are analysis the obtained results using some GROMACS tools and getting radial distribution functions in order to do the mapping to obtain the coarse-grained model.
We have chosen two different ways to construct the coarse-grained model,using two and four beads, grouping the atoms of the sugar rings indifferent configurations. We are using the VOTCA project and IBIsCO software to apply the IBI and IB techniques.
