Sepsis is one of the most important problems of modern medicine. Endotoxins which are the main component of the outer membrane of Gram-negative bacteria play a key role in the development of septic shock entering the bloodstream from the destroyed bacteria cells. By its chemical structure endotoxins are lipopolysaccharides (LPS). The methods of specific blood purification require understanding of the mechanisms of molecular interactions of endotoxins with different sorbents. Computer models of single LPS molecule and of the outer membrane of the Gram-negative bacteria cell wall may help in this situation.
For computer simulations we use explicit solvent molecular dynamics method with the OPLS-AA force field. Because of the high variability of polysaccharides some fragments of LPS molecule are not described in the OPLS-AA force field. For these missing fragments the parameter values are computed using quantum chemistry methods. Partial charges of the atoms located at the junction of fragments fully described in force field are calculated using the RESP procedure. Torsion angle potential parameters are computed by fitting the quantum chemistry potential energy by total molecular mechanical energy.
After computation of all the missing parameters the full atom molecular models of single LPS molecule as well as of outer membrane of Gram-negative bacteria were created. Different spatial configurations of LPS molecules in the membrane were studied by full atom molecular dynamics using supercomputer complex of Moscow State University.