Explicit Solvent Molecular Dynamics

The molecular dynamics approach allows for the simulation of the system components individually with atomic resolution. Broadly speaking, an appropriately constrained Newtonian dynamics is used to capture the evolution of particles representing individual ions, atoms, or groups of atoms in the force field generated by electrostatic and van der Waals interactions together with boundary conditions. One difference between molecular dynamics and Brownian dynamics is the way the solvent is modeled Water molecules are typically treated explicitly within the molecular dynamics framework. 

The role of water in ion permeation through narrow channels was stressed previously a model that accounts for the dynamics of the ionic solvation state is needed for a full understanding of channel functionality. Furthermore, the atomic resolution of molecular dynamics includes sufficient information to (in principle) treat polarization effects with highly accurate. 

Many models are used to include the microscopic effects of water molecules on biological systems, and most of them are based on parameterized force field schemes that are tuned to reproduce some bulk macroscopic properties of the solvent. For a given system, the choice of a specific water model is based on the usual tradeoff between accuracy and computational complexity. Furthermore, even if a particular model fits a type of data better than another— for example, dielectric constant better than density versus temperature—the choice of which model to use is not obvious. 

fixed-charge water models are widely used in molecular dynamics simulations. Their popularity is from their algorithmic simplicity and from their ability to reproduce many thermodynamic properties that match experiment. Within these models, point charges combined with empirical potentials are used to model the electrostatic interaction of the water molecule with its environment. The charges are placed at specific sites within the molecular volume, and the effective potentials are tuned to reproduce the average (bulk) effects of polarization. 

The integration schemes used for Newtonian dynamics are simpler than that employed in the Brownian dynamics simulation based on Langevin s equation (see the section Implicit Solvent Brownian Dynamics ). A popular choice for Newtonian molecular dynamics is the Verlet integration scheme 

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Baptista M (2002) Comment on Explicit-solvent molecular dynamics simulation at constant pH Methodology and application to small amines . J Chem Phys 116 7766-7768. 

Borjesson U, Hiinenberger PH (2004) pH-dependent stability of a decalysine a-helix studied by explicit-solvent molecular dynamics simulations at constant pH. J Phys ChemB 108 13551-13559. 

The importance of water molecules for the structural dynamics and the functioning of ribozymes was investigated by Rhodes and co-workers. They studied non-coded RNA using a combination of explicit solvent molecular dynamics and single molecule fluorescence spectroscopy approaches (Rhodes et al 2006). 

How can one then decide on the choice of the dielectric boundary One possibility is to benchmark PB calculations against explicit-solvent molecular dynamics (MD) simulations. Most of such efforts have been limited to small solute molecules [20-22]. However, it has been shown that the difference between MS and vdW results for electrostatic solvation energies depends on solute size [23]. Therefore parameterization on small solutes (either against explicit-solvent MD results or against experimental data) may not be reliable for calculating electrostatic contributions to protein-protein and protein-nucleic acid binding. 

Validation of the OPLS2.0 force field includes comparison to quantum mechanical energy profiles and experimental solvation free energies. For the latter, we performed explicit solvent molecular dynamics free energy perturbation simulations on a set of 239 diverse small molecules [80]. Compared with other popular force fields... 

Chang R, Yethiraj A (2006) Dilute solutions of strongly charged flexible polyelectrolytes in poor solvents molecular dynamics simulations with explicit solvent. Macromolecules 39 821-828. doi 10.1021/ma051095y... 

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. 

In this chapter we shall consider four important problems in molecular n iudelling. First, v discuss the problem of calculating free energies. We then consider continuum solve models, which enable the effects of the solvent to be incorporated into a calculation witho requiring the solvent molecules to be represented explicitly. Third, we shall consider the simi lation of chemical reactions, including the important technique of ab initio molecular dynamic Finally, we consider how to study the nature of defects in solid-state materials. 

Explicit solvent methods. Monte Carlo methods are somewhat more popular than molecular dynamics methods. 

The molecular dynamics method is useful for calculating the time-dependent properties of an isolated molecule. However, more often, one is interested in the properties of a molecule that is interacting with other molecules. With HyperChem, you can add solvent molecules to the simulation explicitly, but the addition of many solvent molecules will make the simulation much slower. A faster solution is to simulate the motion of the molecule of interest using Langevin dynamics. 

Another way is to reduce the magnitude of the problem by eliminating the explicit solvent degrees of freedom from the calculation and representing them in another way. Methods of this nature, which retain the framework of molecular dynamics but replace the solvent by a variety of simplified models, are discussed in Chapters 7 and 19 of this book. An alternative approach is to move away from Newtonian molecular dynamics toward stochastic dynamics. 

The idea of a finite simulation model subsequently transferred into bulk solvent can be applied to a macromolecule, as shown in Figure 5a. The alchemical transformation is introduced with a molecular dynamics or Monte Carlo simulation for the macromolecule, which is solvated by a limited number of explicit water molecules and otherwise surrounded by vacuum. Then the finite model is transferred into a bulk solvent continuum... 

In the second group come molecular dynamics and Monte Carlo simulations, especially those where the solvent is modelled without being explicitly included. Their fourth class is the related supermolecule class, where we actually include solvent molecules in the simulation, and treat the entire array of molecules according to the rules of quantum mechanics or whatever. 

Presently, only the molecular dynamics approach suffers from a computational bottleneck [58-60]. This stems from the inclusion of thousands of solvent molecules in simulation. By using implicit solvation potentials, in which solvent degrees of freedom are averaged out, the computational problem is eliminated. It is presently an open question whether a potential without explicit solvent can approximate the true potential sufficiently well to qualify as a sound protein folding theory [61]. A toy model study claims that it cannot [62], but like many other negative results, it is of relatively little use as it is based on numerous assumptions, none of which are true in all-atom representations. 

Dimitrov, D. 1., Milchev, A. and Binder, K (2007) Polymer brushes in solvents of variable quality Molecular dynamics simulations using explicit solvent./. Chem. Phys., 127, 084905. 

If all nuclei are assigned and the spectral parameters for the conformational analysis are extracted, a conformation is calculated - usually by distance geometry (DG) or restrained molecular dynamics calculations (rMD). A test for the quality of the conformation, obtained using the experimental restraints, is its stability in a free MD run, i.e. an MD without experimental restraints. In this case, explicit solvents have to be used in the MD calculation. An indication of more than one conformation in fast equilibrium can be found if only parts of the final structure are in agreement with experimental data [3]. Relaxation data and heteronuclear NOEs can also be used to elucidate internal dynamics, but this is beyond the scope of this article. 

Hybrid MPC-MD schemes may be constructed where the mesoscopic dynamics of the bath is coupled to the molecular dynamics of solute species without introducing explicit solute-bath intermolecular forces. In such a hybrid scheme, between multiparticle collision events at times x, solute particles propagate by Newton s equations of motion in the absence of solvent forces. In order to couple solute and bath particles, the solute particles are included in the multiparticle collision step [40]. The above equations describe the dynamics provided the interaction potential is replaced by Vj(rJVs) and interactions between solute and bath particles are neglected. This type of hybrid MD-MPC dynamics also satisfies the conservation laws and preserves phase space volumes. Since bath particles can penetrate solute particles, specific structural solute-bath effects cannot be treated by this rule. However, simulations may be more efficient since the solute-solvent forces do not have to be computed. 

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