# Accelerating high-throughput virtual screening through molecular pool-based active learning

**Authors:** David E. Graff, Eugene I. Shakhnovich, Connor W. Coley  
**arXiv:** [2012.07127](https://arxiv.org/abs/2012.07127)  
**Date:** 2020-12-13  
**Summary page:** https://www.summarizepaper.com/en/paper/2012.07127v1/

## Key points

- Structure-based virtual screening is a crucial tool for identifying potential drug candidates in drug discovery.
- Virtual libraries contain over 100 million molecules, making exhaustive virtual screening campaigns resource-intensive.
- Researchers have turned to Bayesian optimization techniques that leverage surrogate structure-property relationship models to reduce computational costs.
- In a recent study, various surrogate model architectures, acquisition functions and acquisition batch sizes were assessed on several protein-ligand docking datasets.
- Testing only 2.4% of a 100 million member library allowed researchers to identify 87.9% of the top 50 thousand ligands.
- Model-guided searches not only mitigate increasing computational costs but also have applications beyond docking and could accelerate high-throughput virtual screening campaigns in other areas of drug discovery.
- Leveraging machine learning techniques in early stage drug discovery efforts can improve efficiency and reduce costs while maintaining accuracy and reliability in identifying promising compounds for further development.

## Summary

In the field of drug discovery, structure-based virtual screening is a crucial tool for identifying potential drug candidates. However, as virtual libraries continue to expand and contain over 100 million molecules, conducting exhaustive virtual screening campaigns becomes increasingly resource-intensive. To address this challenge, researchers have turned to Bayesian optimization techniques that leverage surrogate structure-property relationship models trained on predicted affinities of a subset of the library. By applying these models to the remaining library members, less promising compounds can be excluded from evaluation, significantly reducing computational costs. In a recent study by David E. Graff, Eugene I. Shakhnovich, and Connor W. Coley titled "Accelerating high-throughput virtual screening through molecular pool-based active learning," various surrogate model architectures, acquisition functions and acquisition batch sizes were assessed on several protein-ligand docking datasets. The results showed significant reductions in computational costs even when using a greedy acquisition strategy. For example, testing only 2.4% of a 100 million member library allowed researchers to identify 87.9% of the top 50 thousand ligands. The authors note that such model-guided searches not only mitigate the increasing computational costs associated with screening large virtual libraries but also have applications beyond docking; this approach could accelerate high-throughput virtual screening campaigns in other areas of drug discovery and lead to more efficient identification of potential drug candidates. Overall, this study highlights the importance of leveraging machine learning techniques in early stage drug discovery efforts to improve efficiency and reduce costs while maintaining accuracy and reliability in identifying promising compounds for further development.