The design of compounds with desirable properties – The anti‐HIV case study

Efficacy and safety are among the most desirable characteristics of an ideal drug. The tremendous increase in computing power and the entry of artificial intelligence into the field of computational drug design are accelerating the process of identifying, developing, and optimizing potential drugs....

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Bibliographic Details
Published in:Journal of computational chemistry 2023-04, Vol.44 (10), p.1016-1030
Main Authors: Novak, Jurica, Pathak, Prateek, Grishina, Maria A., Potemkin, Vladimir A.
Format: Article
Language:English
Subjects:
3CLpro
Algorithms
Artificial Intelligence
Biocompatibility
COVID-19
cytotoxicity
drug repurposing
Genetic algorithms
HIV‐1 protease
Humans
Molecular Docking Simulation
Neural networks
QSAR
Quantitative Structure-Activity Relationship
Reproducibility of Results
Toxicity
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Summary:Efficacy and safety are among the most desirable characteristics of an ideal drug. The tremendous increase in computing power and the entry of artificial intelligence into the field of computational drug design are accelerating the process of identifying, developing, and optimizing potential drugs. Here, we present novel approach to design new molecules with desired properties. We combined various neural networks and linear regression algorithms to build models for cytotoxicity and anti‐HIV activity based on Continual Molecular Interior analysis (CoMIn) and Cinderella's Shoe (CiS) derived molecular descriptors. After validating the reliability of the models, a genetic algorithm was coupled with the Des‐Pot Grid algorithm to generate new molecules from a predefined pool of molecular fragments and predict their bioactivity and cytotoxicity. This combination led to the proposal of 16 hit molecules with high anti‐HIV activity and low cytotoxicity. The anti‐SARS‐CoV‐2 activity of the hits was predicted. By applying machine learning methods, new molecules with desired properties can be designed within a reasonable time frame and with low computational costs. The approach is demonstrated with the development of anti‐HIV compounds with low cytotoxicity.
ISSN:0192-8651
1096-987X
DOI:10.1002/jcc.27061