Molecular Dynamics with Implicit Solvent

Some work has also appeared describing MD with implicit solvation for solutes described at the DFT level. Fattebert and Gygi (2002) have proposed making the external dielectric constant a function of the electron density, thereby achieving a smooth transition from solute to solvent instead of adopting a sudden change in dielectric constant at a particular cavity surface. Non-electrostatic components of the solvation free energy have not been addressed in this model. 

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Noticeable differences in conformation of surfactant lipoprotein assessed via Monte Carte simulation with implicit solvent and molecular dynamics in explicit solvent were observed. 

Quantum chemical methods are well established, accepted and of high potential for investigation of inorganic reaction mechanisms, especially if they can be applied as a fruitful interplay between theory and experiment. In the case of solvent exchange reactions their major deficiency is the limited possibility of including solvent effects. We demonstrated that with recent DFT-and ab initio methods, reaction mechanisms can be successfully explored. To obtain an idea about solvent effects, implicit solvent models can be used in the calculations, when their limitations are kept in mind. In future, more powerful computers will be available and will allow more sophisticated calculations to be performed. This will enable scientists to treat solvent molecules explicitly by ab initio molecular dynamics (e.g., Car-Parrinello simulations). The application of such methods will in turn complement the quantum chemical toolbox for the exploration of solvent and ligand exchange reactions. 

Aiming to describe any kind of time-dependent phenomena, it would be highly desirable to couple the standard molecular dynamics (MD) methods, both classical and ab initio, with the implicit solvent model. This can be achieved either by solving the... 

In order to determine what interactions dominate the optical rotation of methyloxirane in water, Mukhopadhayay et al. [151] have calculated the optical rotation of the solute-solvent system by including an explicit solvent shell in the calculations. Additional calculations were performed on the solvent shell alone, with the methyloxirane removed. Explicit solvent molecules were modeled by molecular dynamics. Implicit solvation was also considered, modeled by the COSMO continuum model. The optical rotation calculations were performed at the BP86/aug-cc-pVDZ level of theory and did not include zero-point vibrational... 

The motions of proteins are usually simulated in aqueous solvent. The water molecules can be represented either explicitly or implicitly. To include water molecules explicitly implies more time-consuming calculations, because the interactions of each protein atom with the water atoms and the water molecules with each other are computed at each integration time step. The most expensive part of the energy and force calculations is the nonbonded interactions because these scale as 77 where N is the number of atoms in the system. Therefore, it is common to neglect nonbonded interactions between atoms separated by more than a defined cut-off ( 10 A). This cut-off is questionable for electrostatic interactions because of their 1/r dependence. Therefore, in molecular dynamics simulations, a Particle Mesh Ewald method is usually used to approximate the long-range electrostatic interactions (71, 72). 

The most expensive part of a simulation of a system with explicit solvent is the computation of the long-range interactions because this scales as Consequently, a model that represents the solvent properties implicitly will considerably reduce the number of degrees of freedom of the system and thus also the computational cost. A variety of implicit water models has been developed for molecular simulations [56-60]. Explicit solvent can be replaced by a dipole-lattice model representation [60] or a continuum Poisson-Boltzmann approach [61], or less accurately, by a generalised Bom (GB) method [62] or semi-empirical model based on solvent accessible surface area [59]. Thermodynamic properties can often be well represented by such models, but dynamic properties suffer from the implicit representation. The molecular nature of the first hydration shell is important for some systems, and consequently, mixed models have been proposed, in which the solute is immersed in an explicit solvent sphere or shell surrounded by an implicit solvent continuum. A boundary potential is added that takes into account the influence of the van der Waals and the electrostatic interactions [63-67]. 

As discussed earlier, EXEDOS simulations can be used to determine free energy differences (or PMF s) with remarkable accuracy. If the reaction coordinate, is chosen to be the end-to-end distance between the N and C termini of the protein molecule being stretched, then the resulting PMF and its derivative should correspond to the actual force measured in the laboratory, provided the molecule is pulled slowly (i.e. reversibly) [32]. In this example, Monte Carlo simulations therefore provide an ideal bound against which results of molecular dynamics can be compared. We present results for a 15-segment polyalanine molecule, which adopts a stable a-helical conformation in an implicit solvent [26]. By applying an external stretching force. 

The SES and ESP approximations include the dynamics of solute degrees of freedom as fully as they would be treated in a gas-phase reaction, but these approximations do not address the full complexity of condensed-phase reactions because they do not allow the solvent to participate in the reaction coordinate. Methods that allow this are said to include nonequilibrium solvation. A variety of ways to include nonequilibrium solvation within the context of an implicit or reduced-degree-of-freedom bath are reviewed elsewhere [69]. Here we simply discuss one very general such NES method [76-78] based on collective solvent coordinates [71, 79]. In this method one replaces the solvent with one or more collective solvent coordinates, whose parameters are fit to bulk solvent properties or molecular dynamics simulations. Then one carries out calculations just as in the gas phase but with these extra one or more degrees of freedom. The advantage of this approach is its simplicity (although there are a few subtle technical details). 

The mean-field effect of the environment can be included in biomolecular simulations simply by adding an expression for the solvation free energy of an instantaneous solute conformation to a given molecular mechanics force field [1]. Such an implicit solvent potential addresses the thermodynamic component of solute-solvent interactions. Kinetic and hydrodynamic properties may be reintroduced through the use of Langevin dynamics where coupling with a temperature bath is implemented through stochastic collisions and solvent friction [2,3,18]. 

Chen, Y.Z., Chen, X., Deng, Y.F. Simulating botuhnum neurotoxin with constant pH molecular dynamics in Generalized Bom implicit solvent. Comput. Phys. Commun. 2007,177,210-3. 

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