Molecular evaluation

This chapter illustrates the characterizations of technical procedures necessary in the course of these molecular evaluations, describing our laboratory experience and suggesting different diagnostic approaches microdissection techniques, extraction of nucleic acids from paraffin-embedded tissues, polymerase chain reaction (PCR), direct sequencing, and allelic separation by cloning [4-7],... 

Colombat P, Salles G, Brousse N, et al. Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden clinical and molecular evaluation. Blood 2001 97 101-106. 

Bury, Y. et al. (2001) Molecular evaluation of vitamin D3 receptor agonists designed for topical treatment of skin diseases. The Journal of Investigative Dermatology, 116, 785-792. 

Coppola, S., Blaiotta, G., Ercohni, D., Moschetti, G. (2001). Molecular evaluation of microbial diversity occurring in different types of mozzareUa cheese. Journal of Applied Microbiology, 90, 414—420. 

After an initial molecular evaluation, a variety of crystal growth strategies are available, but not limited to evaporation and cooling (at varying rates and temperatures), " milling (liquid-assisted or neat), sonication, melting, and reaction crystallization. More non-traditionaf techniques include spray drying, twin-screw extrusion, and supercritical fluids which have all been demonstrated to be scalable processes. 

Williams GD, Christodoulou J, Stack J, et al. Surfactant protein B deficiency clinical, histological and molecular evaluation. J Paediatr Child Health 1999 35(2) 214-220. 

Although distillation and elemental analysis of the fractions provide a good evaluation of the qualities of a crude oil, they are nevertheless insufficient. Indeed, the numerous uses of petroleum demand a detailed molecular analysis. This is true for all distillation fractions, certain crude oils being valued essentially for their light fractions used in motor fuels, others because they make quality lubricating oils and still others because they make excellent base stocks for paving asphalt. 

Furthermore, molecular analysis is absolutely necessary for the petroleum industry in order to interpret the chemical processes being used and to evaluate the efficiency of treatments whether they be thermal or catalytic. This chapter will therefore present physical analytical methods used in the molecular characterization of petroleum. 

The external reflection of infrared radiation can be used to characterize the thickness and orientation of adsorbates on metal surfaces. Buontempo and Rice [153-155] have recently extended this technique to molecules at dielectric surfaces, including Langmuir monolayers at the air-water interface. Analysis of the dichroic ratio, the ratio of reflectivity parallel to the plane of incidence (p-polarization) to that perpendicular to it (.r-polarization) allows evaluation of the molecular orientation in terms of a tilt angle and rotation around the backbone [153]. An example of the p-polarized reflection spectrum for stearyl alcohol is shown in Fig. IV-13. Unfortunately, quantitative analysis of the experimental measurements of the antisymmetric CH2 stretch for heneicosanol [153,155] stearly alcohol [154] and tetracosanoic [156] monolayers is made difflcult by the scatter in the IR peak heights. 

If an ideal solution is formed, then the actual molecular A is just Aav (and Aex = 0). The same result obtains if the components are completely immiscible as illustrated in Fig. IV-21 for a mixture of arachidic acid and a merocyanine dye [116]. These systems are usually distinguished through the mosaic structure seen in microscopic evaluation. 

A more elaborate theoretical approach develops the concept of surface molecular orbitals and proceeds to evaluate various overlap integrals [119]. Calculations for hydrogen on Pt( 111) planes were consistent with flash desorption and LEED data. In general, the greatly increased availability of LEED structures for chemisorbed films has allowed correspondingly detailed theoretical interpretations, as, for example, of the commonly observed (C2 x 2) structure [120] (note also Ref. 121). 

The alternative simulation approaches are based on molecular dynamics calculations. This is conceptually simpler that the Monte Carlo method the equations of motion are solved for a system of A molecules, and periodic boundary conditions are again imposed. This method pennits both the equilibrium and transport properties of the system to be evaluated, essentially by numerically solvmg the equations of motion... 

Dupuis M, Rys J and King H F 1976 Evaluation of molecular integrals over Gaussian basis functions J. Chem. Phys. 65 111-16... 

Kofke D A and Cummings P T 1997 Quantitative comparison and optimization of methods for evaluating the chemical potential by molecular simulation Mol. Phys. 92 973-96... 

Obtaining high-quality nanocry stalline samples is the most important task faced by experimentalists working in tire field of nanoscience. In tire ideal sample, every cluster is crystalline, witli a specific size and shape, and all clusters are identical. Wlrile such unifonnity can be expected from a molecular sample, nanocrystal samples rarely attain tliis level of perfection more typically, tliey consist of a collection of clusters witli a distribution of sizes, shapes and stmctures. In order to evaluate size-dependent properties quantitatively, it is important tliat tire variations between different clusters in a nanocrystal sample be minimized, or, at tire very least, tliat tire range and nature of tire variations be well understood. 

In this chapter, we look at the techniques known as direct, or on-the-fly, molecular dynamics and their application to non-adiabatic processes in photochemistry. In contrast to standard techniques that require a predefined potential energy surface (PES) over which the nuclei move, the PES is provided here by explicit evaluation of the electronic wave function for the states of interest. This makes the method very general and powerful, particularly for the study of polyatomic systems where the calculation of a multidimensional potential function is an impossible task. For a recent review of standard non-adiabatic dynamics methods using analytical PES functions see [1]. 

The gradient of the PES (force) can in principle be calculated by finite difference methods. This is, however, extremely inefficient, requiring many evaluations of the wave function. Gradient methods in quantum chemistiy are fortunately now very advanced, and analytic gradients are available for a wide variety of ab initio methods [123-127]. Note that if the wave function depends on a set of parameters X], for example, the expansion coefficients of the basis functions used to build the orbitals in molecular orbital (MO) theory. 

A final point to be made concerns the symmetry of the molecular system. The branching space vectors in Eqs. (75) and (76) can be obtained by evaluating the derivatives of matrix elements in the adiabatic basis... 

The vibronic coupling model has been applied to a number of molecular systems, and used to evaluate the behavior of wavepackets over coupled surfaces [191]. Recent examples are the radical cation of allene [192,193], and benzene [194] (for further examples see references cited therein). It has also been used to explain the lack of structure in the S2 band of the pyrazine absoiption spectrum [109,173,174,195], and recently to study the photoisomerization of retina] [196],... 

In modem quantum chemistry packages, one can obtain moleculai basis set at the optimized geometry, in which the wave functions of the molecular basis are expanded in terms of a set of orthogonal Gaussian basis set. Therefore, we need to derive efficient fomiulas for calculating the above-mentioned matrix elements, between Gaussian functions of the first and second derivatives of the Coulomb potential ternis, especially the second derivative term that is not available in quantum chemistry packages. Section TV is devoted to the evaluation of these matrix elements. 

Straatsma, T.P, Berendsen, H.J.C. Free energy of ionic hydration Analysis of a thermodynamic integration technique to evaluate free energy differences by molecular dynamics simulations. J. Chem. Phys. 89 (1988) 5876-5886. 

Abstract. Molecular dynamics (MD) simulations of proteins provide descriptions of atomic motions, which allow to relate observable properties of proteins to microscopic processes. Unfortunately, such MD simulations require an enormous amount of computer time and, therefore, are limited to time scales of nanoseconds. We describe first a fast multiple time step structure adapted multipole method (FA-MUSAMM) to speed up the evaluation of the computationally most demanding Coulomb interactions in solvated protein models, secondly an application of this method aiming at a microscopic understanding of single molecule atomic force microscopy experiments, and, thirdly, a new method to predict slow conformational motions at microsecond time scales. 

M. Eichinger, H. Grubmiiller, H. Heller, and P. Tavan. FAMUSAMM An algorithm for rapid evaluation of electrostatic interaction in molecular dynamics simulations. J. Comp. Chem., 18 1729-1749, 1997. 

Very recently, we have developed and incorporated into the CHARMM molecular mechanics program a version of LN that uses direct-force evaluation, rather than linearization, for the fast-force components [91]. The scheme can be used in combination with SHAKE (e.g., for freezing bond lengths) and with periodic boundary conditions. Results for solvated protein and nucleic-... 

Our work is targeted to biomolecular simulation applications, where the objective is to illuminate the structure and function of biological molecules (proteins, enzymes, etc) ranging in size from dozens of atoms to tens of thousands of atoms today, with the desire to increase this limit to millions of atoms in the near future. Such molecular dynamics (MD) simulations simply apply Newton s law to each atom in the system, with the force on each atom being determined by evaluating the gradient of the potential field at each atom s position. The potential includes contributions from bonding forces. 

NAMD [7] was born of frustration with the maintainability of previous locally developed parallel molecular dynamics codes. The primary goal of being able to hand the program down to the next generation of developers is reflected in the acronym NAMD Not (just) Another Molecular Dynamics code. Specific design requirements for NAMD were to run in parallel on the group s then recently purchased workstation cluster [8] and to use the fast multipole algorithm [9] for efficient full electrostatics evaluation as implemented in DPMTA [10]. 

Parallel molecular dynamics codes are distinguished by their methods of dividing the force evaluation workload among the processors (or nodes). The force evaluation is naturally divided into bonded terms, approximating the effects of covalent bonds and involving up to four nearby atoms, and pairwise nonbonded terms, which account for the electrostatic, dispersive, and electronic repulsion interactions between atoms that are not covalently bonded. The nonbonded forces involve interactions between all pairs of particles in the system and hence require time proportional to the square of the number of atoms. Even when neglected outside of a cutoff, nonbonded force evaluations represent the vast majority of work involved in a molecular dynamics simulation. 

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