Free energy calculations of protein-water complexes with Gromacs

Abstract

We used GFP(Green Fluorescent Protein) to understand its basic structure, adding solvent water around the GFP, minimize and equilibrating it using molecular dynamics simulation with Gromacs. Gromacs is an open source software and widely used in molecular dynamics simulation of biological molecules such as proteins, and nucleic acids (DNA AND RNA-molecules). We employ the CHARMM (Chemistry at HARvard Molecular Mechanics) program for the force fields which enable the potential energy of a molecular system to be calculated rapidly. In this particular simple molecular mechanics interaction fields (CHARMM), the force fields consists of stretching energy, bending energy and torsion energy. The non-bond interaction energy is modeled by Lennard-Jones potential. The pdb2gmx gromacs command is implemented to obtained the basic coordinate file and topology for the particular system from the GFP PDB file (1gfl.pdb). We enclosed water molecule in a rhombic dodecahedron box having size 0.5nm, and protein are embedded in solvent water. The steepest descent method (first-order minimization) are implemented to calculate the local energy minimum with 104-steps. The stability of protein with solvent water molecule are analyzed by measuring the root-mean square displacement (RMSD) of all atoms. It was shown with help of figure that RMSD initially increases rapidly in the first part of simulation, but become stable around 0.14nm, roughly the resolution of the X-ray structure. The difference is partly due to the moving and vibration of atoms around an equilibrium structure. Secondary structure of GFP protein is presented with the help of DSSP-program.