THESIS
2021
1 online resource (x, 69 pages) : color illustrations
Abstract
Solvation effect plays a critical role in many chemical and biological processes such as protein
folding and drug delivery. Therefore, understanding the solvation effect is an important task in
computational chemistry to aid rational design of these processes. The state-of-art method to
predict solvation effect is the integration equation theory (IET), which provides good prediction
accuracy at a reasonable computational complexity. Among all IET-based solvation models,
the three-dimensional reference interaction site model (3DRISM) theory is the most developed
one in recent years. When combined with various closures and the universal correction (UC) method, 3DRISM can be applied to compute the hydration free energy and solubility of drug-like molecules. However, when it is employed to...[
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Solvation effect plays a critical role in many chemical and biological processes such as protein
folding and drug delivery. Therefore, understanding the solvation effect is an important task in
computational chemistry to aid rational design of these processes. The state-of-art method to
predict solvation effect is the integration equation theory (IET), which provides good prediction
accuracy at a reasonable computational complexity. Among all IET-based solvation models,
the three-dimensional reference interaction site model (3DRISM) theory is the most developed
one in recent years. When combined with various closures and the universal correction (UC) method, 3DRISM can be applied to compute the hydration free energy and solubility of drug-like molecules. However, when it is employed to predict solvation structures, 3DRISM fails to
accurately obtain the first solvation peaks of water around highly hydrophilic or ionic solute molecules. To address this deficiency, this project developed the ion-dipole correction (IDC) method based on the 3DRISM framework (3DRISM-IDC) to incorporate the strong polarization
of water molecules induced by highly charged solute groups. In particular, it was proposed to
adopt an ensemble average scheme to incorporate the thermodynamic fluctuations of molecular
orientations of water into 3DRISM-IDC. This scheme largely improved the predictions of the
locations and heights of the first solvation peaks and it is expected that the combination of 3DRISM and IDC can provide a generalizable approach to predict solvation structure and thermodynamics of complex chemical and biological molecules.
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