Natural products (NPs), being evolutionary selected to bind to biological macromolecules, remained an important source of inspiration for medicinal chemists even after the advent of efficient drug discovery technologies. Thus, there is a strong demand for efficient and user-friendly computational tools that allow to analyze large libraries of NPs. Over the past 20 years, a lot of scientific reports exhaustively analyzed the chemical space of NPs in the medicinal chemistry context. Most of them, however, simply report static results of particular compound library analysis, without possibility to explore the chemical space of NPs via interactive interface.<br/>In this context, we present NP Navigator – a free, intuitive online tool for visualization and navigation through the NPs chemical space. It is based on the hierarchical ensemble of more than 200 generative topographic maps(GTM), featuring NPs from the COlleCtion of Open NatUral producTs (COCONUT), bioactive compounds from ChEMBL and commercially available molecules from ZINC. Being a nonlinear probabilistic dimensionality reduction method, GTM is well suited to power NP Navigator. It has already proven to be a successful approach for the visualization and analysis of large chemical libraries. Hierarchical extension of GTM, combined with maximum common substructure (MCS) detection, allows to establish the link between the generalized visualization of the known chemical space of NPs/NP-like molecules and structural features of small compound clusters.<br/>As a result, NP Navigator allows to efficiently analyze different aspects of NPs - chemotype distribution, physicochemical properties, reported and/or predicted biological activity and commercial availability of NPs. The latter concerns not only purchasable NPs but also their close analogs that can be considered as pseudo-NPs. Users are welcome not only to browse through hundreds of thousands of compounds from ZINC, ChEMBL and COCONUT but also to project several external molecules that play the role of “chemical trackers” allowing to trace particular chemotypes in the NPs chemical space and detect analogs of the compound of interest. Web-based implementation of NP Navigator is freely accessible by the link - https://infochm.chimie.unistra.fr/npnav/chematlas_userspace.

NP navigator: A new look at the natural product chemical space

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.