Enhanced sampling methods

An overreaching theme of the present chapter, besides broken ergodicity, has to do with the fact that most of the enhanced sampling methods that we shall discuss address situations in which one cannot clearly identify a reaction coordinate that can be conveniently used to describe the kinetic evolution of the system of interest. While methods for enhanced sampling are designed to yield accurate results faster than regular molecular dynamics or Monte Carlo (MC) methods, it is our belief that there is no perfect method, but that, rather, there are methods that perform better for particular applications. Moreover, it should be noted that, while in instances when a proper reaction coordinate can be identified methods described in other chapters are probably more efficient, they could still benefit by sampling in conformational directions perpendicular to the reaction coordinate. 

In such cases, the MEHMC method could be employed in combination with an enhanced sampling method that deforms the effective energy surface (but preserves the location of the potential minima), such as that in [29, 97]. Likewise, it may be worthwhile to explore the use of a reversible multiple-time-scale molecular dynamics propagator [103] with MEHMC to accelerate the dynamical propagation. 

While all enhanced sampling methods, reviewed here or not, are good strategies in themselves because they improve convergence in the calculation of equilibrium... 

Andricioaei, I. Dinner, A.R. Karplus, M., Self-guided enhanced sampling methods for thermodynamic averages, 7. Chem. Phys. 2003,118, 1074—1084... 

Figure 3 The basic locally enhanced sampling method for determining free energy differences through a thermodynamic cycle...

REMD, the authors point to [38], Briefly, REMD is an enhanced sampling method that acts to vary the temperature stochastically through a simulation. This allows for the RNA molecule to sample faster and obtain a more global energy minimum structure. 

Of special importance to AIMD are the enhanced sampling methods termed elastic band and string methods. Michaelides and coworkers explained in their excellent free-energy method assessment article that special considerations have to be taken when rare event simulations are done within AIMD. As the iterative SCF procedure has an impact on the calculation of the forces in contrast to the exact forces in empirical simulations, the convergence tolerance of the SCF procedure has to be chosen carefully, especially for reactive situations [61]. 

Next, difficulties encountered in ab initio molecular dynamics simulations were discussed. Topics covered were massive parallelization to address computer time problems, basis set considerations, density functionals and van der Waals interactions, relativistic corrections, and new integration schemes. Several simulation techniques used to gain chemical insight were summarized. Enhanced sampling methods, metadynamics and other methods to explore free energy surfaces, reaction pathways and transition states were covered. Simulation of spectra (IR, NMR, EXAFS) from ab initio molecular dynamics simulations was the subject of the remaining paragraphs. 

Enhanced Sampling Methods Replica Exchange Molecular Dynamics... 

Sinko W, Lindert S, McCammon JA (2013) Accounting for receptor flexibility and enhanced sampling methods in computer-aided drug design. Chem Biol Drug Des 81(l) 41-49. doi 10.1111/cbdd.l2051... 

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