Discrete water molecules

Many molecular mechanics potentials were developed at a time when it was computationally impractical to add large numbers of discrete water molecules to the calculation to simulate the effect of aqueous media. As such, techniques came into place that were intended to take into account the effect of solvent in some fashion. These techniques were difficult to justify physically but they were used nevertheless. 

Many ionic compounds can have water molecules incorporated into their solid structures. Such compounds are called hydrates. To emphasize the presence of discrete water molecules in the chemical structure, the formula of any hydrate shows the waters of hydration separated from the rest of the chemical formula by a dot. A coefficient before H2 O indicates the number of water molecules in the formula. Copper(II) sulfate pentahydrate is a good example. The formula of this beautiful deep blue solid is C11SO4 5 H2 O, indicating that five water molecules are associated with each CuSOq unit. Upon prolonged heating, CuSOq 5 H2 O loses its waters of hydration along with its color. Other examples of hydrates include aluminum nitrate nonahydrate, A1 (N03)3 9 H2 O,... 

Luecke, H. (2000) Atomic resolution structures of bacterio-rhodopsin photocycle intermediates the role of discrete water molecules in the function of this light-driven ion pump. Biochim. Biophys. Acta 1460, 133-156. 

The problem to be solved was this. Along each O O there must, at any instant, be only one proton and it must be 0.96 A from one oxygen atom and 1.80 A from the other. To each oxygen atom, at any instant, only two hydrogen atoms may be covalently bonded ( 0.96 A), thus constituting a discrete water molecule. Each such water molecule must act as acceptor for hydrogen bonds from the two other neighbouring molecules. These constraints have to be reconciled with the symmetry of the ice crystal. 

For attack of F on acrylic acid, first a hydrogen bonded complex is formed which then proceeds to the transition state and then to a stable carbanion. The methyl in the methacrylic acid reduces stabilization of the carbanion as predicted. Subsequent studies using ammonia as the nucleophile indicated that attack proceeded by a rate-determining intramolecular proton transfer from the nucleophile to the ligand, assisted by a discrete water molecule that acts as a catalyst17. They predicted that acrolein underwent 1,4-addition, acrylic acid either 1,2- or 1,4-addition and acrylonitrile 1,2-addition. 

Rarey, M., Kramer, B., and Lengauer, T. (1999) The particle concept placing discrete water molecules during protein-ligand docking predictions. Proteins 34,17-28. 

The Particle Concept Placing Discrete Water Molecules During Protein-Ligand Docking Predictions. 

SCHEME 8.R.3 Using the curved arrow method to describe the reaction that forms H30 and OH in water. As indicated by the two arrows at the bottom of the drawing, the process is reversible and goes in both directions, what chemists call a dynamic equilibrium. The longer backwards arrow indicates that, at any given time, the concentration of discrete water molecules is larger than that of the ions. 

M. Rarey, B. Kramer, and T. Lengauei Proteins Struct., Pune., Genet., 34, 17 (1999). The Particle Concept Placing Discrete Water Molecules During Protein-Ligand Docking Predictions. 

The Koopmans ionization potential of methyl mercaptan and its thiolate anion were calculated with the 6-3IG basis set. Results found for the calculated ionization potential of the anion at the 6-31 + G(d) level deviated more significantly from the experimental value than those obtained in the absence of diffuse functions. Consequently, diffuse functions were not employed. The calculated corrected solution-ionization energy of the thiolate anion hydrated with three discrete water molecules was found to be in very good agreement with the experimental value (5.4eV vs. 5.7 0.2eV). In Figure 8 we show the effect of stepwise hydration on the IP of the methyl thiolate... 

An accurate description of the aqueous environment is essential for atom-level biomolec-ular simulations, but may become very expensive computationally. An imphcit model replaces the discrete water molecules by an infinite continuum medium with some of the dielectric and hydrophobic properties of water. The continuum implicit solvent models have several advantages over the explicit water representation, especially in molecular dynamics simulations (e.g., they are often less expensive, and generally scale better on parallel machines they correspond to instantaneous solvent dielectric response the continuum model corresponds to solvation in an infinite volume of solvent, there are no artifacts of periodic boundary conditions estimating free energies of solvated structares is much more straightforward than with explicit water models). Despite the fact that the methodology represents an approximation at a fundamental level, it has in many cases been successful in calculating various macromolecular properties (Case et al. 2005). 

Since n transition energies of these states in (1) gas-phase, (2) with discrete water molecules, and (3) and (4) in the presence of bulk solvent with two dielectric constant values e = 7.0 and 78.4, respectively, for TNI and their adiabatic states. As an example, the plot of the variation of transition energies of 7T a(5 -P04) with increasing solvation is shown in O Fig. 34-18. From O Fig. 34-18, it is evident that transition energies for the increase with increasing solvation and... 

Structural waters in and around protein recognition sites. Impact of the second-order contributions. Discrete water molecules, whether individually or in arrays, are considered to be an integral part of protein or NA structures. We summarize below recent findings aiming to unravel the impact of polarization and charge-transfer on the stabilization energies they confer. These studies bore on superoxide dismutase (SOD), a bimetallic Zn/Cu metaUoenzyme, and on the complexes of inhibitors with the FAK tyrosine kinase and with the PMI Zn-metaUoenzyme. 

Van Duijnen et al. in a set of papers have developed a version of a QM/classical approach in which classical solvent (water) molecules are treated as point polarizable dipoles. The portion of space with discrete water molecules is kept small and surrounded by a continuum dielectric. More attention is paid here to boundary conditions. The method makes use of a direct reaction field (RF) (in contrast with almost all other continuum methods which use an averaged RF) the average is given later with the aid of MC calculations, where the classical particles are also provided with a repulsive potential to avoid collapse of the particles. Not many details are given, however. 

Life in an aqueous environment can be treated at three levels. We first of all have the so-called water structure which arises from the peculiar intermolecular nature of water and which is perturbed by pressure, temperature and solutes. At the molecular level, we must examine discrete water molecules in protein crystals or in polysaccharides to see how they act in stabilizing or destabilizing certain structures. Then we have, on a more macroscopic level, water as a transport medium that distributes nutrients and carries waste products away this is a fascinating study in itself. Then, finally, there is water as the physical environment for many living organisms in oceans, rivers and lakes. Many organisms live all their lives in water, and the physical properties of water have really shaped the development of such organisms in no small amount. 

The spontaneous hydrolysis of a series of triatyl and diall l aiyl phosphate esters (204) (Scheme 67), previously studied experimentally, has been examined theoretically using two different hybrid density functional methods, B3LYP and M06, and the Gaussian 09 program. The B3LYP/ 6 —31- -G(d) methodology combined excellent accuracy with minor computational cost, and the calculations showed excellent quantitative agreement with experiment, which was best in the presence of three discrete water molecules. ... 

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