J Chem Inf Model - Searching for substructures in fragment spaces.

Tópicos

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Resumo

A common task in drug development is the selection of compounds fulfilling specific structural features from a large data pool. While several methods that iteratively search through such data sets exist, their application is limited compared to the infinite character of molecular space. The introduction of the concept of fragment spaces (FSs), which are composed of molecular fragments and their connection rules, made the representation of large combinatorial data sets feasible. At the same time, search algorithms face the problem of structural features spanning over multiple fragments. Due to the combinatorial nature of FSs, an enumeration of all products is impossible. In order to overcome these time and storage issues, we present a method that is able to find substructures in FSs without explicit product enumeration. This is accomplished by splitting substructures into subsubstructures and mapping them onto fragments with respect to fragment connectivity rules. The method has been evaluated on three different drug discovery scenarios considering the exploration of a molecule class, the elaboration of decoration patterns for a molecular core, and the exhaustive query for peptides in FSs. FSs can be searched in seconds, and found products contain novel compounds not present in the PubChem database which may serve as hints for new lead structures.

Resumo Limpo

common task drug develop select compound fulfil specif structur featur larg data pool sever method iter search data set exist applic limit compar infinit charact molecular space introduct concept fragment space fss compos molecular fragment connect rule made represent larg combinatori data set feasibl time search algorithm face problem structur featur span multipl fragment due combinatori natur fss enumer product imposs order overcom time storag issu present method abl find substructur fss without explicit product enumer accomplish split substructur subsubstructur map onto fragment respect fragment connect rule method evalu three differ drug discoveri scenario consid explor molecul class elabor decor pattern molecular core exhaust queri peptid fss fss can search second found product contain novel compound present pubchem databas may serv hint new lead structur

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