Molecular Diversity Assessment using Chemotypes / Hugo O. Villar, Raghav Mandayan, Mark R. Hansen

Background: Many techniques to design chemical libraries for screening have been putforward over time. General use libraries are still important when screening against novel targets,and their design has relied on the use of molecular descriptors. In contrast, chemotype or scaffoldanalysis has been used less often. Objective: We describe a simple method to assess chemical diversity based on counts of the chemotypesthat offers an alternative to model chemical diversity. We describe a simple method to assesschemical diversity based on counts of the chemotypes that offers an alternative to model chemicaldiversity based on computed molecular properties. We show how chemotype counts can be used toevaluate the diversity of a library and compare diversity selection algorithms. We demonstrate anefficient compound selection algorithm based on chemotype analysis. Methods: We use automated chemotype perception algorithms and compare them to traditionaltechniques for diversity analysis to check their effectiveness in designing diverse libraries forscreening. Results: The best type of molecular fingerprints for diversity selection in our analysis are extendedcircular fingerprints, but they can be outperformed by the use of a chemotype diversity algorithm,which can be more intuitive than traditional techniques based on molecular descriptors. Chemotype--based algorithms retrieve a larger share of the chemotypes contained in a library when picking asubset of the chemicals in a collection. Conclusions: Chemotype analysis offers an alternative for the generation of a general-purposescreening library as it maximizes the number of chemotypes present in a subset with the smallestnumber of compounds. The applications of methods based on chemotype analysis that does not resortto the use of molecular descriptors are a very promising but seldom explored area of chemoinformatics.

Medienart:	E-Artikel

Erscheinungsjahr:	2021
Erschienen:	2021

Enthalten in:	Zur Gesamtaufnahme - volume:18
Enthalten in:	Current computer-aided drug design - 18(2021), 1, Seite 8

Sprache:	Englisch

Beteiligte Personen:	Villar, Hugo O. [VerfasserIn] Mandayan, Raghav [VerfasserIn] Hansen, Mark R. [VerfasserIn]

Links:	FID Access [lizenzpflichtig]

Umfang:	1 Online-Ressource (8 p)

Förderinstitution / Projekttitel:

PPN (Katalog-ID):	KFL011155914