Chemistry Reference
In-Depth Information
continuum solvent assumed outside a cavity is constructed around the solute
molecule. The polarization of the continuum screens the electric field arising from
nuclei and electron distribution. The surface charge density on the boundary
represents the effects of polarization. The entire effect of dielectric polarization is
described by screening charges arising on the interface. Cavity surface and solute
describe the local system (problem) [578].
Non-polar contributions (hydrophobic effects), van der Waals interactions
between receptor and ligand due to solvation and strain energies (conformation
reorganization energy performed with full MM-PBSA method). Changes in solute
entropy upon binding determined by single static structures or conformational
ensembles. Single point calculations (SP/MM-PBSA), an ensemble of
configurations or a combination of structural models, explicit solvent and MD
simulations combined with continuum solvent models.
The LIE approach considers the linear combination of electrostatic and van der
Waals interaction energies between environment and the ligand considering the
free solvated ligand and the ligand bound to a solvated receptor. This approach
can be used in combination with MD, MC/MD and energy minimization. It is
taken into consideration hydrogen bonds between ligand and surroundings;
accepted or donated, apolar, aromatic or polar ligand SASA; receptor SASA and
ligand or receptor intramolecular energy; chemical functionality in the ligand as
well a number of ligand rotable bonds [579].
COSMO-RS and COSMO-SAC are extensions of dielectric continuum-solvation
models to liquid-phase thermodynamics, which requires input in the form of a
molecule-specific distribution of the surface-charge density. The molecule placed
in a cavity, with its exact size, within a homogeneous medium or solvent. The
solvation free energy can be determined from the sum of the cavity-forming free
energy and the charging free energy. The cavity-formation free energy is the
change in Gibbs energy to form a cavity in a solution S of the exact size of the
molecule. Charging free energy is the Gibbs energy to remove the screening
charges from the surface of the molecule [578].
