Molecular dynamics simulations electrostatic free energies

This method avoids the convergence and accuracy problems of molecular dynamics or Monte Carlo simulations of systems containing explicit solvent molecules, by evaluating the electrostatic free energy of just one solute conformation surrounded by a dielectric continuum, and by adding the surface term and an estimate of the loss of the configurational entropy upon binding.77... 

The atomic radii may be further refined to improve the agreement between experimental and theoretical solvation free energies. Work on this direction has been done by Luque and Orozco (see [66] and references cited therein) while Barone et al. [67] defined a set of rules to estimate atomic radii. Further discussion on this point can be found in the review by Tomasi and co-workers [15], It must be noted that the parameterization of atomic radii on the basis of a good experiment-theory agreement of solvation energies is problematic because of the difficulty to separate electrostatic and non-electrostatic terms. The comparison of continuum calculations with statistical simulations provides another way to check the validity of cavity definition. A comparison between continuum and classical Monte Carlo simulations was reported by Costa-Cabral et al. [68] in the early 1980s and more recently, molecular dynamics simulations using combined quantum mechanics and molecular mechanics (QM/MM) force-fields have been carried out to analyze the case of water molecule in liquid water [69],... 

The Poisson equation can be solved for the electrostatic potential using finite difference techniques [23,24]. Such calculations are straightforward but relatively expensive [25]. There has been recent progress in improving the accuracy of solvation free energies from Poisson theory [26], but the computational cost for solving the Poisson equation directly at each simulation step in a molecular dynamics simulation has remained prohibitive. 

Over the recent years implicit solvent models have undergone a transition to relatively mature methodology that is now widely employed in molecular dynamics simulations and related applications. Most popular are implicit solvent models based on a decomposition of the solvation free energy into electrostatic and nonpolar components. The electrostatic free energy is typically obtained according to a continuum electrostatics model that is described by Poisson theory or by the more approximate but much more efficient Generalized Born formalism. 

Molecular Dynamics Simulations With rapid evaluation of energies and gradients, molecular dynamics (MD) simulations can be carried out. For MD simulations in the gas phase, the complex was first heated to 300 K by 6,000 steps and equilibrated at that temperature for 100 ps. Then, a 5-ns NVE trajectory was generated by free dynamics. The time step was 0.1 fs to follow the fast proton motions. For simulations in explicit solvent, a 46.0 A x 46.0 A x 40.9 A box of CDCI3 was first generated with a density of 1.50 g/cm. The Pt[Cl2(6-DPPon)2l complex was then solvated and periodic boundary conditions were applied. A cutoff of 12 A was applied to the shifted electrostatic and switched van der Waals interactions. Before 1-ns free dynamics simulations, the system was heated to 300 K and then equilibrated for 10 time steps. 

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