Abstract
To explore the athermal effect of an external electrostatic field on the stabilities of protein conformations and the binding affinities of protein-protein/ligand interactions, the dependences of the polar and hydrophobic interactions on the external electrostatic field, −Eext, were studied using molecular dynamics (MD) simulations. By decomposing Eext into, along, and perpendicular to the direction formed by the two solutes, the effect of Eext on the interactions between these two solutes can be estimated based on the effects from these two components. Eext was applied along the direction of the electric dipole formed by two solutes with opposite charges. The attractive interaction free energy between these two solutes decreased for solutes treated as point charges. In contrast, the attractive interaction free energy between these two solutes increased, as observed by MD simulations, for Eext = 40 or 60 MV/cm. Eext was applied perpendicular to the direction of the electric dipole formed by these two solutes. The attractive interaction free energy was increased for Eext = 100 MV/cm as a result of dielectric saturation. The force on the solutes along the direction of Eext computed from MD simulations was greater than that estimated from a continuum solvent in which the solutes were treated as point charges. To explore the hydrophobic interactions, Eext was applied to a water cluster containing two neutral solutes. The repulsive force between these solutes was decreased/increased for Eext along/perpendicular to the direction of the electric dipole formed by these two solutes.
Highlights
Among the four fundamental interactions, the electrostatic force dominates non-covalent bond interactions between atoms in biomolecules such as proteins, DNA, and RNA
The results showed that the depth of the first well of potential of mean force (PMF)(two_atoms; EXext = 40 or 60 MV/cm) was deeper than that of PMF(two_atoms; EXext = 0) (Figure 4c)
FYnet(two_atoms; EYext) was compared to the force on solute S2 in Figure 3a with external electrostatic fields EY = 50 MV/cm and 100 MV/cm; (c) EYext was applied to a water cluster containing S2; (d) The force on S2 was contributed by the polarized water molecules in the space occupied by S1
Summary
Among the four fundamental interactions, the electrostatic force dominates non-covalent bond interactions between atoms in biomolecules such as proteins, DNA, and RNA. For one or two charged atoms in a spherical water cluster, the dependence of the electric dipole of TIP3P water on the net electrostatic field at the oxygen atom of TIP3P water, and the dependence of the radial distribution function of TIP3P water on the mean force at the oxygen atom of TIP3P water, have been explored [33,37,38] In this project, the source code of the Charmm package [39] was modified, and it was verified that it can be applied to an external electrostatic field. The external electrostatic field along the x or y direction (EXext, EYext) was applied to a water cluster containing one or two charged atoms, and the dependences of the mean force and the potential of mean force (PMF) between the charged solutes on Eext were studied using MD simulations [40]. The differences between the mean force estimated from a continuum solvent and that computed using MD simulations were discussed
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