Electrostatic Screening in Molecular Dynamics Simulations

Abstract

The screened Coulombic potential has been shown to describe satisfactorily equilibrium properties like pA" shifts, the effects of charged groups on redox potentials and binding constants of metal ions. To test how well the screening of the electrostatic potential describes the dynamical trajectory of a macromolecular system, a series of comparative simulations have been carried out on a protein system which explicitly included water molecules and a system in vacuo. For the system without solvent the results of using (i) the standard potential form were compared with results of (ii) the potential where the Coulomb term was modified by the inclusion of a distance dependent dielectric, e(r), to model the screening effect of bulk water, and (iii) standard potential modified by reducing the charge on ionized residue side chains. All molecular dynamics simulations have been carried out on bovine pancreatic trypsin inhibitor. Comparisons between the resulting trajectories, averaged structures, hydrogen bonding patterns and properties such as solvent accessible surface area and radius of gyration are described. The results show that the dynamical behaviour of the protein calculated with a screened electrostatic term compares more favourably with the time-dependent structural changes of the full system with explicitly included water than the standard vacuum simulation.

EasyMIFs and SiteHound: a toolkit for the identification of ligand-binding sites in protein structures

“…The parameters for the Lennard-Jones term, representing the van der Waals interactions, depend on the chosen probe and the particular protein atom type, and are taken from a matrix of parameters distributed with the GROMACS package (Van Der Spoel et al, 2005). The distancedependent dielectric sigmoidal function of Solmajer and Mehler (1991) as described in Cui et al (2008) is used. The default output is a 1 Å resolution grid with dimensions large enough to accommodate the entire protein.…”

Automated identification of binding sites for phosphorylated ligands in protein structures

“…The Molecular Interaction Field (MIF) calculations were performed with our program EasyMIFs,10 which uses the nonbonded component of the GROMOS force field (G43b1, in vacuo) as made available in the GROMACS11 package with a distance‐dependent dielectric derived from Solmajer and Mehler 12. The program computes the potential energy between a chemical probe (represented by a particular atom type) and the protein on a regularly spaced grid, using the following equation: where the potential energy calculated for a probe at a point i in the grid is equal to the sum of a Lennard‐Jones and an electrostatics term over all the atoms of the protein.…”

“…The dielectric constant $ {1 \over {4\pi {\varepsilon} _0 }} $ has been set to 138.935485, as done in the GROMACS package and reported in the GROMACS manual 13. The distance‐dependent dielectric sigmoidal function has been taken from Solmajer and Mehler12 and has the following form: where A = 6.02944; B = e 0 – A ; e 0 = 78.4; λ = 0.018733345; k = 213.5782. When the distance between the probe and an atom becomes less than 1.32 Å, a dielectric constant of 8 is used.…”

Prediction of polyelectrolyte polypeptide structures using Monte Carlo conformational search methods with implicit solvation modeling

“…In order to establish the appropriate value of eo in Equation 4, we considered values of 1,4,10,40, and 80 (such values have been used for implicit modeling of bulk solvent effects on mechanistic and dynamic simulations [Warshel & Russell, 1984, 1985Matthew, 1985;Harvey, 1989;Solmajer & Mehler, 1991;Lee et al, 19931). The use of Equation 4 with = 1 will overestimate electrostatic forces (Smith & Pettitt, 1992, 1994), whereas eo = 80 should underestimate these forces (Matthew, 1985).…”