Template-based collective variables

The topomeric procedure described above attempts to circumvent the alignment problem that plagues most field-based QSAR techniques. While the assumption that template-based combinatorial compounds can be aligned with respect to their common core is certainly a reasonable one, it is not as clear how this technique could be used to compare multiple libraries or heterogeneous compound collections, or even libraries where the template itself is a variable site (a synthetic approach that is becoming quite common). 

Therefore, because proteins generally exist as one of several recurrent structural motifs, it is plausible to use a CV that is a similarity measure with minimal building blocks of one of those motifs. One then evaluates the number of times this building block is present in the actual MD snapshot. This is the central idea behind the template-based collective variables of Pietrucci and Laio. °... 

The behavior of RNA polymerases at sites of DNA damage can best be understood by using site-specific, modified DNA templates in which the precise location, base linkage site, and stereochemistry of the lesion is known. Studies using this approach have collectively shown that the capacity of a DNA lesion to block transcription is a function of several interrelated variables, which have been summarized in prior articles and still hold true [11, 12, 33, 34]. These parameters include the structure of the specific RNA polymerase s active site, the size and shape of the DNA adduct, the stereochemistry of the adduct, the particular base incorporated into the growing transcript at the site of the damage, and the local DNA sequence. 

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