The importance of atomic partial charges in the reproduction of intermolecular interactions for the triacetin - a model of glycerol backbone.

Lipids play a central role within the cell. They not only encompass it but are also engaged in many processes such as cellular transport and energy production. Despite ongoing advances in experimental studies, computer simulations are a viable method to trace their behavior at the atomic level and on an elusive time scale. In molecular modeling studies, the quality of the obtained results is associated with the considered force field and its parameters. In the present work, the authors have investigated the procedure of partial charges fitting on the example of a triacetin molecule, containing chemical moieties present in the glycerol backbone. The goal of the study was to validate assigned partial charges based on the quality of the torsion profiles using optimally assigned torsional coefficients and reproduction of the condensed phase properties of triacetin. We applied various approaches and noticed a significant improvement in the parameterization of triacetin compared to the original one. The results showed that it is important to take into account the intermolecular interactions in the partial charges fitting procedure to obtain good quality validation results.

Condensed phase properties of n-pentadecane emerging from application of biomolecular force fields.

For over 20 years, the OPLS-All Atom (OPLS-AA) force field has been efficiently used in molecular modelling studies of proteins, carbohydrates and nucleic acids. OPLS-AA is successfully applied in computer modelling of many organic compounds, including decane and shorter alkanes, but it fails when employed for longer linear alkanes, whose chemical structure corresponds to hydrocarbon tails in phospholipids constituting cellular membranes. There have been several attempts to address this problem. In this work, we compare the ability to reproduce various condensed phase properties by six distinct sets of force field parameters which can be assigned to phospholipid hydrocarbon chains. In this comparison, we include three alternative sets of the OPLS-AA force field, as well as the commonly used CHARMM C36, Slipids, and Berger lipids' parameters.

Refined OPLS all-atom force field parameters for n-pentadecane, methyl acetate, and dimethyl phosphate.

OPLS All-Atom (OPLS/AA) is a generic all-atom force field which was fine-tuned to accurately reproduce condensed phase properties of organic liquids. Its application in modeling of lipid membranes is, however, limited mainly due to the inability to correctly describe phase behavior and organization of the hydrophobic core of the model lipid bilayers. Here we report new OPLS/AA parameters for n-pentadecane, methyl acetate, and dimethyl phosphate anion. For the new force field parameters, we show very good agreement between calculated and numerous reference data, including liquid density, enthalpy of vaporization, free energy of hydration, and selected transport properties. The new OPLS/AA parameters have been used in successful submicrosecond MD simulations of bilayers made of bacterial glycolipids whose results will be published elsewhere shortly.