Field-based approaches

More detailed aspects of protein function can be obtained also by force-field based approaches. Whereas protein function requires protein dynamics, no experimental technique can observe it directly on an atomic scale, and motions have to be simulated by molecular dynamics (MD) simulations. Also free energy differences (e.g. between binding energies of different protein ligands) can be characterised by MD simulations. Molecular mechanics or molecular dynamics based approaches are also necessary for homology modelling and for structure refinement in X-ray crystallography and NMR structure determination. 

Because the AIMS method associates a unique nuclear wavefunction with each electronic state, one has direct access to dynamical quantities on individual states. This is unlike mean-field based approaches that use only one nuclear wavefunction for all electronic states [59]. One can therefore calculate branching ratios... 

Equation 2.74 is a general form that is used in a number of field-based approaches to 3-D molecular alignment and similarity. For example, in the program Seal (64) the coefficients given either in Eq. 2.73 or Eq. 2.74 are subsumed into a single property coefficient, a /> => wtJ, which may account for the effect of multiple types of properties,... 

The surface energy y(hkl) can be defined as the energy needed to create a unit surface area by cutting the infinite crystal into two parts and by allowing surface relaxation to occur. We recall the definition given by Gay and Rohl (55) in a force field-based approach ... 

As described in the Introduction, it is usually possible to consider the modeling of experimental data separately from the scheme actually used to move atoms about. Ideally, the different models should be able to be used in the different minimization or dynamics schemes. Thus, the subsequent sections describe the kind of data offered by NMR and the kinds of penalty functions or pseudo-energy terms that can be used to represent them. For convenience, we use nomenclature common to force field-based approaches where one refers to a distance constraint potential Vdc r) as a function of intemudear distance. 

RNA and DNA are in general very difficult to model with force-field based approaches. One major difficulty is to reproduce the backbone conformation (crucial for any modeling of nucleic acids), as the corresponding torsional energy barriers are very small [29]. First results from AIMD are encouraging the calculated structure of a hydrated GpG RNA duplex in laboratory realizable conditions (that is, in the crystal phase)[25] showed excellent agreement with experiment and provided the H-bond network postulated by the crystallographers. 

Sdabola, S., Alex, A., Higginson, P.D., Mitchell, J.C., Snowden, M.J. and Morao, I. (2005) Theoretical prediction of the enantiomeric excess in asymmetric catalysis. An alignment-independent molecular interaction field based approach. J. Org. Chem., 70, 9025-9027. 

D fingerprint Tanimoto similarity of the hits confirmed that the field-based approaches were better at scaffold hopping and delivered more diverse hits. 

Mesoscopic methods include several field-based approaches such as cell dynamical systems (CDS), mesoscale density functional theory (DFT), and self-consistent field (SCF)" theory. Most of these methods are related to the time-dependent Ginzburg-Landau equation (TDGL) ... 

The electric charge or polarity of cells (and cell contents) may also be used for manipulation and transportation within microfluidic devices. In contrast to mechanical methods, the use of electric field based approaches such as electrokinetics and dielectrophoresis are well-suited for microfluidics as they permit flexibility, controllability, automation and high-throughput capability. We note, however, that these kinds of techniques can produce undesired biological stress such as protein migration and clustering within the cells and in high fields, cells may... 

The Flory-Huggins theory (a mean field based approach) and statistical thermodynamic approaches based on the Debye-Hiickel theory are the two most frequently used approaches. In the Debye-Hiickel approach, the interactions between charges of the same sign cause intramolecular self-repulsion influencing the PE interaction and structure. 

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