Dielectric-Properties of Trypsin-Inhibitor and Lysozyme Calculated From Molecular-Dynamics Simulations

The static and frequency dependent dielectric properties of trypsin inhibitor and hen egg white lysozyme have been calculated from the fluctuations in the total dipole moment of the two proteins. Total dipole moment fluctuations were obtained from long molecular dynamics simulations of both proteins in an explicit solvent environment. Despite differences in the total charge, volume, shape and secondary structure composition of the two proteins, consistent values for the dielectric constant were obtained. The static dielectric constant of trypsin inhibitor was calculated to be 36, compared with a value of 30 for hen egg white lysozyme. Convergence in the calculations required 1 ns of simulation. The calculated frequency dependent dielectric constant was also consistent with known experimental dielectric dispersion curves for proteins in aqueous solution. The implications for free energy calculations involving significant charge redistribution are also discussed

Solvent-dependent conformation and hydrogen-bonding capacity of cyclosporin A: Evidence from partition coefficients and molecular dynamics simulations

The partition coefficient of cyclosprin A (CsA) was measured in octanol/water and heptane/water by centrifugal partition chromatography. By comparison with results from model compounds, it was deduced that the hydrogen-bonding capacity of CsA changed dramatically from an apolar solvent (where it is internally H-bonded) to polar solvents (where it exposes its H-bonding groups to the solvent). Molecular dynamics simulations in water and CCl4 support the suggestion that CsA undergoes a solvent-dependent conformational changes and that the interconversion process is slow on the molecular dynamics time scale