Molecular dynamics simulation explicit solvent models

The explicit definition of water molecules seems to be the best way to represent the bulk properties of the solvent correctly. If only a thin layer of explicitly defined solvent molecules is used (due to hmited computational resources), difficulties may rise to reproduce the bulk behavior of water, especially near the border with the vacuum. Even with the definition of a full solvent environment the results depend on the model used for this purpose. In the relative simple case of TIP3P and SPC, which are widely and successfully used, the atoms of the water molecule have fixed charges and fixed relative orientation. Even without internal motions and the charge polarization ability, TIP3P reproduces the bulk properties of water quite well. For a further discussion of other available solvent models, readers are referred to Chapter VII, Section 1.3.2 of the Handbook. Unfortunately, the more sophisticated the water models are (to reproduce the physical properties and thermodynamics of this outstanding solvent correctly), the more impractical they are for being used within molecular dynamics simulations. 

Solvent effects can significantly influence the function and reactivity of organic molecules.1 Because of the complexity and size of the molecular system, it presents a great challenge in theoretical chemistry to accurately calculate the rates for complex reactions in solution. Although continuum solvation models that treat the solvent as a structureless medium with a characteristic dielectric constant have been successfully used for studying solvent effects,2,3 these methods do not provide detailed information on specific intermolecular interactions. An alternative approach is to use statistical mechanical Monte Carlo and molecular dynamics simulation to model solute-solvent interactions explicitly.4 8 In this article, we review a combined quantum mechanical and molecular mechanical (QM/MM) method that couples molecular orbital and valence bond theories, called the MOVB method, to determine the free energy reaction profiles, or potentials of mean force (PMF), for chemical reactions in solution. We apply the combined QM-MOVB/MM method to... 

NMR spectroscopy is a very useful tool for determining the local chemical surroundings of various atoms. Komin et al studied theoretically this for the adenine molecule of Fig. 20 both in vacuum and in an aqueous solution using different computational approaches. In all cases, density-functional calculations were used for the adenine molecule, but as basis functions they used either a set of localized functions (marked loc in Table 45) or plane waves (marked pw). Furthermore, in order to include the effects of the solvent they used either the polarizable continuum approach (marked PCM) or an explicit QM/MM model with a force field for the solvent and a molecular-dynamics approach for optimizing the structure (marked MD). In that case, the chemical shifts were calculated as averages over 40 snapshots from the molecular-dynamics simulations. Finally, in one case, an extra external potential from the solvent acting on the solute was included, too, marked by the asterisk in the table. 

Since the dielectric continuum representation of the solvent has significant limitations, the molecular dynamics simulation of PCET with explicit solvent molecules is also an important direction. One approach is to utilize a multistate VB model with explicit solvent interactions [34-36] and to incorporate transitions among the adiabatic mixed electronic/proton vibrational states with the Molecular Dynamics with Quantum Transitions (MDQT) surface hopping method [39, 40]. The MDQT method has already been applied to a one-dimensional model PCET system [39]. The advantage of this approach for PCET reactions is that it is valid in the adiabatic and non-adiatic limits as well as in the intermediate regime. Furthermore, this approach is applicable to PCET in proteins as well as in solution. 

Specific solute-solvent interactions, which are not explicitly taken into account in continuum models, can play a significant role especially for charged species. A typical cluster formed by the glycine anion radical with four water molecules is shown in figure 16. The analogous supermolecule obtained for the neutral form is quite similar, except for the much weaker interaction energies involved in the neutral species. The number and the position of the solvent molecules are determined by molecular dynamics simulations performed by the AMBER force field [141]. 

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