Biomolecular simulations, water models

A flexible, three-center model labeled F3C has been compared with other water models within the context of biomolecular simulations. This model contains a smooth truncation function acting on all interactions, so dielectric properties may not be well represented. This model stabilizes the hydrogen bond network, as evident from the oxygen-oxygen radial distribution functions, suggesting that the correct local ordering of liquid water is reproduced. A version of this model with a different truncation scheme has also been evaluated. " ... 

Proper condensed phase simulations require that the non-bond interactions between different portions of the system under study be properly balanced. In biomolecular simulations this balance must occur between the solvent-solvent (e.g., water-water), solvent-solute (e.g., water-protein), and solute-solute (e.g., protein intramolecular) interactions [18,21]. Having such a balance is essential for proper partitioning of molecules or parts of molecules in different environments. For example, if the solvent-solute interaction of a glutamine side chain were overestimated, there would be a tendency for the side chain to move into and interact with the solvent. The first step in obtaining this balance is the treatment of the solvent-solvent interactions. The majority of biomolecular simulations are performed using the TIP3P [81] and SPC/E [82] water models. 

H.W. Horn et al., Development of an improved four-site water model for biomolecular simulations TIP4P-Ew. J. Chem. Phys. 120, 9665 (2004)... 

These classical interaction potentials must be parameterized, e.g. the magnitude of the partial charges on each atom in the molecule must be assigned, and the equilibrium bond length and size of the harmonic force constant must be attached to each bond. In the early biomolecular MM forcefields, these parameters were developed to produce molecular models that could reproduce known experimental properties of the bulk system. For example, several MM water models have been developed. ° One of the earliest successful models, TIP3P, was parameterized such that simulations of boxes of TIP3P molecules reproduced known thermodynamic properties of water, such as liquid density and heats of vaporisation. Such a parameterisation scheme is to be applauded, as it ties the molecular model closely to experiment. Indeed many of the common MM models of amino acids were developed by comparison to experiment, e.g. OPLS. Indeed it is such a good... 

CHOOSING AN APPROPRIATE WATER MODEL FOR USE IN BIOMOLECULAR SIMULATIONS... 

Early biomolecular simulations were carried out either in vacuum or in an environment of fixed dielectric constant in order to reduce the computational expense. In most modern simulations, water is explicitly included in order to describe the system as completely as possible. In some cases, such as very large protein systems, for example myosin," it remains necessary to use one of a range of so-called implicit solvent models such as ACE. ... 

Molecular modeling and computer simulation with empirical potential energy function (force field) are now routinely carried out to help understand and predict structures and dynamics of proteins and other macromolecules of biological relevance in water and membrane environments. After over 40 years of development, popular force fields such as AMBER, CHARMM, OPLS and GROMOS have been widely employed in biomolecular simulations. These force fields are used dominantly in highly optimized molecular dynamics... 

Below we show how the appearance of spanning water networks may be detected in computer simulations. In particular, a percolation transition of water upon hydration was studied by simulations in model lysozyme powders and on the surface of a single lysozyme molecule. In protein crystals, increase in hydration of a biomolecular surface may be achieved by applying pressure. In some hydration range, pressurization leads to the formation of spanning water networks enveloping the surface of each biomolecule. Finally, the formation of the spanning water network is shown for the DNA molecule at various conformations and for different forms of DNA. 

Third, as the size and complexity of the biomolecular systems at hand further expand, there are more uncertainties in the molecular model itself. For example, the resolution of the X-ray structure may not be sufficiently high for identifying the locations of critical water molecules, ions and other components in the system the oxidation states and/or titration states of key reactive groups might be unclear. In those cases, it is important to couple QM/MM to other molecular simulation techniques to establish and to validate the microscopic models before elaborate calculations on the reactive mechanisms are investigated. In this context, pKa and various spectroscopic calculations [113,114] can be very relevant. 

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