Locally enhanced sampling

Also in the early 1990s, a somewhat related method for calculating free energy differences was proposed by Ron Elber and coworkers [92, 93]. It relies on simulating multiple, noninteracting replicas that differ only locally. As a result, the method is applicable to systems that undergo only local modification - e.g., point mutations in proteins. For this reason, it has been called the locally enhanced sampling (LES) technique. 

Roitberg, A. Elber, R., Modeling side chains in peptides and proteins application of the locally enhanced sampling technique and the simulated annealing methods to find minimum energy conformations, J. Chem. Phys. 1991, 95, 9277-9287... 

Verkhivker, G. Elber, R. Nowak, W., Locally enhanced sampling in free energy calculations application of mean held approximation to accurate calculation of free energy differences, J. Chem. Phys. 1992, 97, 7838-7841... 

Ulitsky, A. Elber, R., Application of the locally enhanced sampling (LES) and a mean-held with a binary collision correction (CLES) to the simulation of Ar diffusion and NO recombination in myoglobin, J. Phys. Chem. 1994, 98, 1034-1043... 

Simmerling, C. Fox, T. Koliman, P.A., Use of locally enhanced sampling in free energy calculations Testing and application to the alpha — beta anomerization of glucose, J. Am. Chem. Soc. 1998,120, 5771-5782... 

Molecular dynamics and minimization of proteins locally enhanced sampling and free energy calculations along reaction paths by perturbation or thermodynamic integration. Stardent, Silicon Graphics, IBM, and HP workstations, moil-view for visualization of shaded spheres and sticks on Silicon Graphics. Available by anonymous ftp from 128.248.186.70. 

In the multiple copy MD [77] or locally enhance sampling (LES) [78] method, part of the system simulated is replicated multiple times, e.g. 20 copies of a peptide are simulated in the presence of 1 copy of the solvent. There are no interactions between the multiple copies. The unreplicated atoms feel the mean force of all the copies of the replicated atoms. The mean field generated by the multiple copy ensemble reduces the energy barriers but conserves the global energy minimum [78]. The number of degrees of freedom is reduced in the sense that one simulation with m copies of a subset of the atoms samples to a similar extent to m standard simulations (without multiple copies) in approximately l/m times the simulation time. Applications to peptides in solvent have shown improved sampling of phase space [79, 66]. 

Li, H.Z., Fajer, M., Yang, W. Simulated scaling method for localized enhanced sampling and simultaneous "alchemical" free energy simulations A general method for molecular mechanical, quantum mechanical, and quantum mechanical/molecular mechanical simulations. J. Chem. Phys. 2007,126, 024106. 

A. Ulitsky and R. Elber. The equilibrium of the time dependent Hartree and the locally enhanced sampling approximations Formal properties, corrections, and computational studies of rare gas clusters. J. Chem. Phys. 98, 3380 (1993). 

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

In our lab we are happy with the NAMD code (Phillips et al. 2005). It is well documented, relatively fast, well maintained, frequently updated and scales nicely. It has certain flexibility in selection of the force field (CHARMM, AMBER). The authors have implemented Locally Enhanced Sampling (LES), Implicit Ligand Sampling (ILS), Replica Exchange, and Steered Molecular Dynamics (SMD) schemes. New versions of NAMD will run on a GPU, and there are also some attempts to port this code to a computational grid environment. 

Orlowski> S.> Nowak, W. (2007). Locally enhanced sampling molecular dynamics study of the dioxygen transport in human cytoglobin./owrwa/ of Molecular Modeling, 13, 715. 

CBMC = configurational bias Monte Carlo DEM = diffusion equation method LES = locally enhanced sampling QMA = quantum mechanical annealing. 

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