Biomolecular simulations, quantum mechanical

In a series of papers, Stock and coworkers have combined the quasiclassi-cal techniques used in the description of gas phase reactions with biomolecular force fields used in molecular dynamics (MD) simulations. This leads to nonequilibrium MD simulations, which mimic the laser excitation of the molecules by nonequilibrium phase-space initial condition for the solute and the solvent atoms. This approach is based on the following assumptions. Firstly, it is assumed that an empirical force field at least provides a qualitative modeling of the process. This is because the initial relaxation appears to be an ultrafast and generic process and because it can be expected that the strong interaction with the polar solvent smoothes out many details of the intramolecular force field. Secondly, quantum-mechanical effects are only included via the nonequilibrium initial conditions of the classical simulations. This means that the method represents a short-time approximation of quantum mechanics. 

The predictive power of computer simulation relies heavily on the accuracy offeree field and the efficiency of phase space sampling. The broader and comprehensive applications of biomolecular simulation have highlighted the limitations of the existing force fields, and there is an urgent need to develop next generation force field that includes electrostatic polarization for biomolecules. The desired polarizable or polarized force fields should be ideally based on quantum mechanical calculations of biomolecules, which is a challenging task for computational chemists. 

In contrast to large biomolecules where the dynamical behavior can be characterized by large-amplitude conformational changes for smaller molecules the dynamical aspects deal more about translational and rotational motion at much shorter time scales. Translational and rotational diffusion can be studied with both MD and NMR relaxation studies. Also, quantum mechanical studies and ab initio MD simulations become feasible for small molecules. Also hydration can be studied in more details compared to that in large biomolecular systems. 

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