Enhanced Sampling LES

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. 

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... 

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]. 

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

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. 

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

Kay LE, Xu G-Y, Singer AU, Muhandiram DR, Forman-Kay JD. A gradient-enhanced HCCH-TOCSY experiment for recording side-chain 3H and 13C correlations in H20 samples of proteins. J Magn Reson 1993 101B 333-337. 

Two-photon photoemission spectroscopy is known for its capability to reveal not only occupied but also unoccupied electronic density of states [10]. In this scheme, one photon excites an electron below the Fermi level to an intermediate state. A second photon then excites the electron from the intermediate state to a final state above the vacuum le vel. The photoelectron yields are strongly enhanced if the excitation photon energy is tuned to the resonance conditions, and the photoelectron spectrum reflects the electron lifetime in the intermediate states as well as their density of states. It is necessary to keep the employed photon energy below the work function of the sample, otherwise one photon photoemission signal becomes excessive and buries the 2PPE signals. 

The ease of incorporating funchonal groups to modify the pSi surface for mass spectrometric application has allowed for the development of a convenient and simple method for enriching the concentration of analytes. This technique, termed DIOS solid-liquid extraction (SLE), uses the property of differential adsorption selectively to capture analytes from a solution containing contaminants that impede MS analysis. Hydrophobically modified DIOS surfaces could be readily used selectively to remove interferences prior to analysis. DIOS S LE simply involves the deposition of a droplet containing analytes onto the chemically modified DIOS surface then, after approximately 3 s, the sample is aspirated with the same pipette. This short-term deposition allows for any molecule with a propensity to be adsorbed onto the surface to attach itself, while any potential hydrophilic contaminants such as salts and buffers will remain in solution, leaving the surface free from such contaminants. The van der Waals interaction between the analyte and surface leads to a selective extraction of the small molecules, while the hydrophilic contaminants such as salts are removed with the droplet. The DIOS analysis of peptides and small molecules from complex matrices is greatly enhanced by differential adsorption [47]. 

GC X GC produces an orthogonal two-column separation, with the complete sample transfer achieved by means of a modulator the latter entraps, refocuses, and releases fractions of the GC ef uent from the D, onto the D column, in a continuous mode this method enables an accurate screening of complex matrices, offering very high resolution and enhanced detection sensitivity [112,113]. The two columns must possess different separation mechanism, commonly a low polarity or nonpolar column is used in the D, and a polar column is used as the fast D column. Moreover, a 2D separation can be de ned as comprehensive if other two conditions are respected [114,115] equal percentages (either 100% or les of all sample components pass through both columns and eventually reach the detector and the resolution obtained in the D is essentially maintained. 

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