Profile Methods

Fig, 10.25 The six environment categories used by the 3D profiles method. (Figure adapted from Bowie j U, R Liith. and D Eisenberg 1991. A Method to Identify Protein Sequences That Fold into a Known Three-Dunensinnal Structure. Science 253 164-170.)... 

For each fold one searches for the best alignment of the target sequence that would be compatible with the fold the core should comprise hydrophobic residues and polar residues should be on the outside, predicted helical and strand regions should be aligned to corresponding secondary structure elements in the fold, and so on. In order to match a sequence alignment to a fold, Eisenberg developed a rapid method called the 3D profile method. The environment of each residue position in the known 3D structure is characterized on the basis of three properties (1) the area of the side chain that is buried by other protein atoms, (2) the fraction of side chain area that is covered by polar atoms, and (3) the secondary stmcture, which is classified in three states helix, sheet, and coil. The residue positions are rather arbitrarily divided into six classes by properties 1 and 2, which in combination with property 3 yields 18 environmental classes. This classification of environments enables a protein structure to be coded by a sequence in an 18-letter alphabet, in which each letter represents the environmental class of a residue position. 

In this last chapter we cover techniques for measuring surfece areas, surfece roughness, and surface and thin-fdm magnetism. In addition, the effects that sputter-induced surface roughness has on depth profiling methods are discussed. 

Kerns, E. H., Di, L., Pemsky, S., Kleintop, T., Huryn, D., McConnell, O., Carter, G. Pharmaceutical profiling method for lipophilidty and integrity using liquid chromatography-mass spectrometry. 

Thomson J, Higgs NC, Clayton T (1995) A geochemical criterion for the recognition of Heinrich events and estimation of their depositional fluxes by the ( °Thexcess)° profiling method. Earth Planet Sci Lett 135 41-56... 

The profiling method requires the sensitive slice to be shifted through the object. Figure 2.4.2 shows the mechanical lift used to move the sensor with respect to the sample. The object under study, for instance the lower surface of the arm in the picture, is positioned on top of a flat holder (A) and the NMR sensor is placed under it on a movable plate (B). The mechanical construction allows one to move the sensor up and down with a precision of 10 pm. The distance between the rf coil and the sensitive slice defines the maximum penetration depth into the sample (maximum field of view of the ID image). Depending on the application, the position of the rf coil with respect to the sensitive slice can be changed to maximize the sensitivity. 

Figure 6.1. Phylogenetic profile method. Four genomes are shown, each containing a subset of proteins (PI, .P7). The presence or absence of a protein is given by 1 or 0 in the phylogenetic profile shown at lower left. Identical profiles are shown clustered on the right. In this example, the P2 and P7 are functionally linked because they exhibit the same phylogenetic profile. The P3 and P6 protein are similarly linked. Figure adapted from Pellegrini et al. (1999).

Harnly JM, Bhagwat S and Lin LZ. 2007. Profiling methods for the determination of phenolic compounds in foods and dietary supplements. Anal Bioanal Chem 389(1 ) 47—61. 

Summing up the strengths and weaknesses of the 15N profiling method for hydrogen, on the positive side we have the following points ... 

Profile methods have some inherent problems. These are discussed in the following sections. 

The final round scores from iterative profile methods do not reflect the real significance of the match to the query sequence. The significance says how likely the protein segment matches to the profile constructed in the previous round. For example, if a false-positive match with an E... 

A generic problem with profile methods that iterate is the possibility of profile wander (also called matrix migration). This occurs when sequences found in early rounds of the iterative search are not found in later rounds of the search. This problem affects both PSI-BLAST and HMMER. This means that one should record all the intermediate steps so that these lost members of the family can be recovered. Profile wander only becomes a problem for large protein families, and therefore the cause of the profile wander may be related to the limits of modeling using profiles. 

Over the years there have been considerable improvements in the available sequence analysis techniques. In particular the sequence profile method [3] with its more recent extension to generalized profiles [4], and various fJidden Mar-... 

It is worthwhile to restate that the target of the method development is to maximize the separation of the critical pair, not the separation of all components from each other, as would be the case for a stability-indicating impurity profile method. The capacity factor k ) should be in the range of 1 to 5 to avoid the potential for coelution with early eluting compounds or impractical mn times. 

Espina V, Mueller C (2012) Reduction of pre-analytical variability in specimen procurement for molecular profiling. Methods Mol Biol 823 49-57... 

Erdy DM. 1989. The confidence profile method a Bayesian method for assessing health technologies. Operations Res 37 210-228. 

For minerals, if diffusion is anisotropic, the bulk method gives only an average diffusivity for an assumed effective shape, but cannot determine the diffusivity along different crystallographic directions. The profiling method is necessary to quantitatively resolve the anisotropy. 

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