MOLECULAR DYNAMICS SIMULATIONS OF SUPERCRITICAL CO₂: STRUCTURAL AND THERMODYNAMIC ANALYSIS FOR POTENTIAL APPLICATIONS IN BIOPHYSICS

Supercritical fluids are substances maintained above their critical temperature and pressure, exhibiting properties intermediate between liquids and gases. Supercritical carbon dioxide (CO₂) stands out for being non-toxic, non-flammable, and easy to handle, while presenting high diffusivity, low viscosity, and a density comparable to that of liquids. These characteristics make it a promising solvent for applications in biophysics, such as the extraction and modification of biomolecules, drug encapsulation, and the study of molecular interactions. In this work, Molecular Dynamics (MD) simulations were employed to investigate the behavior of supercritical CO₂ under controlled thermodynamic conditions, with the aim of validating simulation parameters and assessing its potential as a model solvent. The modeling and preparation of the CO₂ box were carried out in VMD, using CHARMM force field parameters. Simulations were performed in NAMD, in a box containing 2,197 molecules, within the NPT ensemble at 400 K and 250 bar, extended up to 410 K, and in the NVT ensemble for the calculation of transport properties, with a production run of 2 million steps per simulation. Analyses included the determination of density, which showed a relative error of about 8% compared with NIST data, with values close to those of liquids. A decrease in density with small temperature variations was observed, highlighting the thermal sensitivity of supercritical fluids. Internal energy was calculated, allowing the determination of enthalpy and heat capacity at constant pressure, with an average error of 7% against reference data. The Radial Distribution Function (RDF) showed peaks and interatomic distances consistent with the literature, validating the simulated structure. From the mean square displacement (MSD), a self-diffusion coefficient was obtained with values compatible with reported data for supercritical CO₂ under similar conditions. The results demonstrate that MD is a robust tool for characterizing structural and thermodynamic properties of supercritical solvents, enabling detailed analyses and direct comparisons with experimental data. It is concluded that the employed method allows the construction of consistent models capable of reproducing macroscopic properties with controlled errors, showing promise for studies of biomolecular interactions in alternative solvents.