Fully atomistic simulations

An interesting variant of fully atomistic simulations arises when rigid sections of the model mesogen are replaced by simpler potentials. Cross and Fung [111] have replaced the biphenyl core of some n-alkylcyanobiphenyls with a large... 

These experiments have motivated us to carry out fully atomistic simulation of micelle water systems (details are provided in Appendix A). In Figure 2.2(b) and (c), we show the solvation d)mamics of cesium ions near... 

The best (albeit rather laborious) existing method to study packing in the crystalline phase of a polymer and predict pc relatively accurately is to use fully atomistic simulations. A major... 

Finally, it is highly desirable to improve the ability to calculate the properties of surfaces and interfaces involving polymers by means of fully atomistic simulations. Such simulations can, potentially, account for much finer details of the chemical structure of a surface than can be expected from simulations on a coarser scale. It is, currently, difficult to obtain quantitatively accurate surface tensions and interfacial tensions for polymers (perhaps with the exception of flexible, saturated hydrocarbon polymers) from atomistic simulations, because of the limitations on the accessible time and length scales [49-51]. It is already possible, however, to obtain very useful qualitative insights as well as predictions of relative trends for problems as complex as the strength and the molecular mechanisms of adhesion of crosslinked epoxy resins [52], Gradual improvements towards quantitative accuracy can also be anticipated in the future. 

In summary, the MRG-CG procedure is a systematic and reliable general approach to optimizing the interactions potentials for DNA and ions, reproducing important physical observables that characterize the Hamiltonian itself. This, in turn, leads to the similarity of the structural fluctuations of the macromolecule obtained from the CG and fully atomistic simulations. Application of this technique to coarse-graining DNA molecules resulted in a model that can be used reliably describe the DNA s structural dynamics, including complex anharmonic local deformations of the DNA chains. Likewise, this model also accurately describes the distribution of mobile ions around the DNA molecules and reproduces the experimentally measured dependence of DNA chain s persistence length on the solution ionic strength. 

The main limitation of fully atomistic simulations currently is the timescale that is feasible to explore in MD simulations, usually in the lO-lOOns range, in relation to the timescales for most relaxation and diffusion processes that are of interest in pharmaceutical systems. A representative example of the timescale problem is provided in Figure 13.12 where log-log plots of the mean squared displacements versus time for water and indomethacm diffusion in amorphous IMC containing 0.6% w/w water are shown at temperatures above T (i.e., at 400K compared to the simulated T of 384 K) and well below T (i.e., 298 K). 

Fully atomistic simulations are the most realistic of the three simulation methods. They include a fully detailed description of the amino acids comprising the protein, and they are thus much more true to life than the other models. In addition, solvent molecules may be added explicitly or implicitly to the simulation. Because of this extreme detail, a simulation of a small protein may require the treatment of thousands of atoms. Fully atomic simulations are thus extremely computationally expensive, and only short time scales can be explored. As computational power continues to increase, so do the time scales accessible with this method. Nevertheless, fully atomic simulations still cannot capture kinetic information they are, however, useful in understanding important local interactions that drive protein folding. 

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