Visualizing and Analyzing the Chemical Space of Natural Product Databases for Drug Discovery

Summary

Here, we provide a methodology that uses different molecular representations to display and analyze the chemical space of natural compound data sets, with a focus on applications related to drug discovery.

Abstract

Chemical space is a multidimensional descriptor space that encloses all possible molecules, and at least 1 x 10⁶⁰ organic substances with a molecular weight below 500 Da are thought to be potentially relevant for drug discovery. Natural products have been the primary source of the new pharmacological entities marketed during the past forty years and continue to be one of the most productive sources for the creation of innovative medications. Chemoinformatics-based computational tools accelerate the drug development process for natural products. Methods including estimating bioactivities, safety profiles, ADME, and natural product likeness measurement have been used. Here, we go over recent developments in chemoinformatic tools designed to visualize, characterize, and expand the chemical space of natural compound data sets using various molecular representations, create visual representations of such spaces, and investigate structure-property relationships within chemical spaces. With an emphasis on drug discovery applications, we evaluate the open-source databases BIOFACQUIM and PeruNPDB as proof of concept.

Introduction

Natural products (NPs), which are chemical compounds created by living things, have been utilized as traditional treatments for centuries. Individual NPs have been created as medications in the modern era and successfully exploited as lead compounds in drug discovery¹. Marine, fungal, bacterial, plant, and endogenous substances created by humans and animals are included in the category of bioactive compounds, as are venoms and poisons produced by various animals². As a result, for forty years, the number of medications made by NPs represented a significant source of new pharmacological substances³....

Protocol

1. Software download and installation

1. Make this project's directory fresh. For convenient access, put the executables and files in this directory.
2. Install the required software packages after downloading them.
3. Download the latest version of The Osiris DataWarrior (OSIRIS) software, which can be found at https://openmolecules.org/datawarrior/
4. Download the latest version of The Konstanz Information Miner (KNIME) Analytics Platform, which can be found at ht.......

Discussion

Due to its many potential uses, such as compound classification, compound selection, exploring structure-activity links, and navigating through structure-property interactions, the concept of chemical space is nowadays widely employed in the drug discovery and development process¹⁴. Also, the creation of NP databases is a fundamental procedure to perform various computational studies, including the design of chemical libraries, characterization and comparison of the chemical space, the study of SA.......

Materials

Name	Company	Catalog Number	Comments
GraphPad Prism	GraphPad Prism	https://www.graphpad.com/
KNIME platform	KNIME	https://www.knime.com
Osiris DataWarrior (OSIRIS) software	openmolecules.org	https://openmolecules.org/datawarrior/
PUMA	PUMA: Platform for Unified Molecular Analysis	http://132.248.103.152:3838/PUMA/