Approaches for enhancing the analysis of chemical space for drug discovery

ABSTRACT

Introduction

Chemical space is a general conceptual framework that addresses the diversity of molecules and it has various applications. Moreover, chemical space is a cornerstone of chemoinformatics. In response to the increase in the set of chemical compounds in databases, generators of chemical structures, and tools to calculate molecular descriptors, novel approaches to generate visual representations of chemical space are emerging and evolving.

Areas covered

The current state of chemical space in drug design and discovery is reviewed. The topics discussed herein include advances for efficient navigation in chemical space, the use of this concept in assessing the diversity of different data sets, exploring structure-property/activity relationships for one or multiple endpoints, and compound library design. Recent advances in methodologies for generating visual representations of chemical space have been highlighted, thereby emphasizing open-source methods.

Expert opinion

Quantitative and qualitative generation and analysis of chemical space require novel approaches for handling the increasing number of molecules and their information available in chemical databases (including emerging ultra-large libraries). Chemical space is a conceptual framework that goes beyond visual representation in low dimensions. However, the graphical representation of chemical space has several practical applications in drug discovery and beyond.

KEYWORDS:

• Artificial intelligence
• chemical space
• chemoinformatics
• data visualization
• drug discovery
• structure-activity relationships

Article highlights

• Chemical space is a foundational concept in chemoinformatics, and has numerous practical applications in drug discovery and other areas in chemistry.

• Applications of chemical space include compound selection and design, diversity, and structure-property (activity) relationships analysis.

• Molecular representation is a key feature in studying chemical space quantitatively and qualitatively.

• Novel methods for visualizing chemical spaces are continuously evolving in response to the emerging evolution of large and ultra-large chemical libraries.

• Innovative techniques must be developed to study non-traditional chemical spaces such as large macrocycles, peptides, and metallodrugs.

This box summarizes key points contained in the article.

Declaration of Interest

FI. Saldívar-González was awarded a scholarship grant (no. 848061) from the Consejo Nacional de Ciencia y Tecnología (CONACYT). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors acknowledge grant support from the General Direction of Academic Staff Affairs (DGAPA), UNAM, Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica (UNAM-DGAPA-PAPIIT), grant IN201321.