Applications to Molecular Dynamics

1 Molecular Dynamics of Small Spin-labeled Molecules in Simple FMds. 

Small molecules such as perdeuterated TEMPONE (PDT) and 3-doxylcholes-tane (CSL) were the first nitroxides for which rotational dynamics were characterized in detail by multifrequency EPR at 9 and 250 Onz. These studies permitted an initial exploration of the sensitivity of HF EPR to anisotropy of rotational diffusion and also allowed Freed and co-workers to test diffusion models critically. In order to explain the multifrequency EPR data, the rotational diffusion model has had to be extended from an axial approximation to the fully anisotropic case. This required some modifications of the existing fast- 

Consequent work of Smirnova et al. demonstrated the utility of the multifrequency EPR approach to study molecular dynamics of spin labels with complex superhyperfine shf) structure. Correction for shf, especially if it is poorly resolved, is a challenging task in EPR spectroscopy and typically requires parallel NMR and/or ENDOR experiments. It has been shown that a proper combination of fast motion X-band and W-band EPR data with a convolution-based fitting algorithm eliminates the need for analysis of shfP 

The multifrequency approach has been further exploited by Britton et al. in a study of model lubricants. The study was carried out using specially synthesized spin probes with shapes matching those of the lubricant molecules. Multifrequency EPR measurements of the rotational diffusion tensor for an approximately cylindrical spin probe have shown that the motion of the probe in a cylindrically-shaped, low-traction fluid, 5-(n-octyl)naphthalene, is more anisotropic than in toluene. Thus, a proper matching of the shape of the spin probes with that of the fluid is required.  

One recent example is a HF EPR study of nitroxide side-chain dynamics in a helix-forming peptide which was labeled with MTSSL. The experimental spectra recorded at 140 GHz from 277 to 306 K were found to be amenable to 

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H. Rabitz, Sensitivity analysis Theory with applications to molecular dynamics and kinetics. Computers and Chemistry, 5 (1980) 167-180. 

For quasirigid molecules a symmetry concept has been used very early in some branches of molecular research, e.g. stereochemistry2,3 This symmetry concept was based on the concept of isometric mappings4) and formed the basis of extended applications to molecular dynamics since 1930, developed first by Wigner5). 

MacKerell AD, Jr, NK Banavali (2000) All-atom empirical force field for nucleic acids II. Application to molecular dynamics simulations of DNA and RNA in solution. J. Comput. Chem. 21 (2) 105-120... 

In [112] the insight and accuracy of the approach has been demonstrated it has been extended afterwards to a series of molecules in view of perspective applications to molecular dynamics modeling of collision induced chirality changing processes. 

Derivation and Assessment of a New Set of Ab Initio Potentials and Its Application to Molecular Dynamics Simulations of Biological Molecules in Vacuo, in Crystal and in Aqueous Solution (M. Aida)... 

R. M. Levy, M. Karplus, J. Kushick, and D. Perahia, Macromolecules, 17, 1370 (1984). Evaluation of Configurational Entropy for Proteins Application to Molecular Dynamics Simulations of ct-Helix. 

J. D. Turner, P. K. Weiner, H. M. Chun, V. Lupi, S. Gallion, and U. C. Singh. Variable reduction techniques applied to molecular dynamics simulations. In W. F. van Gunsteren, P. K. Weiner, and A. J. Wilkinson, editors. Computer Simulation of Biomolecular Systems Theoretical and Experimental Applications, volume 2, chapter 24. ESCOM, Leiden, The Netherlands, 1993. 

Although, the notion of molecular dynamics was known in the early turn of the century, the first conscious effort in the use of computer for molecular dynamics simulation was made by Alder and Wainright, who in their paper [1] reported the application of molecular dynamics to realistic particle systems. Using hard spheres potential and fastest computers at the time, they were able to simulate systems of 32 to 108 atoms in 10 to 30 hours. Since the work of Alder and Wainright, interests in MD have increased tremendously, see... 

An important though deman ding book. Topics include statistical mechanics, Monte Carlo sim illation s. et uilibrium and non -ec iiilibrium molecular dynamics, an aly sis of calculation al results, and applications of methods to problems in liquid dynamics. The authors also discuss and compare many algorithms used in force field simulations. Includes a microfiche containing dozens of Fortran-77 subroutines relevant to molecular dynamics and liquid simulations. 

A particularly important application of molecular dynamics, often in conjunction with the simulated annealing method, is in the refinement of X-ray and NMR data to determine the three-dimensional structures of large biological molecules such as proteins. The aim of such refinement is to determine the conformation (or conformations) that best explain the experimental data. A modified form of molecular dynamics called restrained moleculai dynarrdcs is usually used in which additional terms, called penalty functions, are added tc the potential energy function. These extra terms have the effect of penalising conformations... 

CM Clore, AT Bifinger, M Karplus, AM Gronenborn. Application of molecular dynamics with mterproton distance restraints to 3D protein structure determination. J Mol Biol 191 523-551, 1986. 

A review is given of the application of Molecular Dynamics (MD) computer simulation to complex molecular systems. Three topics are treated in particular the computation of free energy from simulations, applied to the prediction of the binding constant of an inhibitor to the enzyme dihydrofolate reductase the use of MD simulations in structural refinements based on two-dimensional high-resolution nuclear magnetic resonance data, applied to the lac repressor headpiece the simulation of a hydrated lipid bilayer in atomic detail. The latter shows a rather diffuse structure of the hydrophilic head group layer with considerable local compensation of charge density. 

The field of electrochemical ion transfer reactions (EITRs) is relatively recent compared with that of electron transfer reactions, and the application of molecular dynamics simulations to study this phenomenon dates from the 1990s. The simulations may shed light on various aspects of the EITR. One of the key questions on this problem is if EITR can be interpreted in the same grounds as those employed to understand electron transfer reactions (ETRs). Eor example, let us consider the electrochemical oxidation reaction of iodine ... 

Chapuisat, X., Natus, A., and Brunet, J.-P. (1991), Exact Quantum Molecular Hamiltonians. Part I. Application to the Dynamics of Three Particles, Mol. Phys. 72,1. 

Encouraging progress has been made recently, and we are now in an era of active application of molecular dynamics simulation to study the folding process. Because of the vital importance of water in protein folding and in the cell, the explicit repre-... 

In addition to the development of new methods, new applications of molecular dynamics computer simulation are also needed in order to make comparisons with experimental results. In particular, more complicated chemical reactions, beyond the relatively simple electron transfer reaction, could be studied. Examples include the study of chemical adsorption, hydrogen evolution reactions, and chemical modification of the electrode surface. All of the above directions and opportunities promise to keep this area of research very active ... 

Time-Local Quantum Master Equations and their Applications to Dissipative Dynamics and Molecular Wires... 

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