# Accelerating Antimicrobial Discovery with Controllable Deep Generative Models and Molecular Dynamics

arXiv: https://arxiv.org/abs/2005.11248 · HTML: https://mlsanity.com/paper/2005.11248/

## Key facts

- Cited by 7 papers in the map (data through 14 Oct 2026).
- First posted on arXiv 22 May 2020.

## Built on by (most cited first, 7 of 7)

- [Reprogramming Pretrained Language Models for Protein Sequence Representation Learning](https://mlsanity.com/paper/2301.02120/) (2023)
- [Sample-Efficient Generation of Novel Photo-acid Generator Molecules using a Deep Generative Model](https://mlsanity.com/paper/2112.01625/) (2021)
- [A molecular generative model with genetic algorithm and tree search for cancer samples](https://mlsanity.com/paper/2112.08959/) (2021)
- [Graph-Based Active Machine Learning Method for Diverse and Novel Antimicrobial Peptides Generation and Selection](https://mlsanity.com/paper/2209.13518/) (2022)
- [Accelerating Antimicrobial Peptide Discovery with Latent Structure](https://mlsanity.com/paper/2212.09450/) (2022)
- [HMAMP: Hypervolume-Driven Multi-Objective Antimicrobial Peptides Design](https://mlsanity.com/paper/2405.00753/) (2024)
- [PepCompass: Navigating peptide embedding spaces using Riemannian Geometry](https://mlsanity.com/paper/2510.01988/) (2025)

## Abstract (arXiv)

De novo therapeutic design is challenged by a vast chemical repertoire and multiple constraints, e.g., high broad-spectrum potency and low toxicity. We propose CLaSS (Controlled Latent attribute Space Sampling) - an efficient computational method for attribute-controlled generation of molecules, which leverages guidance from classifiers trained on an informative latent space of molecules modeled using a deep generative autoencoder. We screen the generated molecules for additional key attributes by using deep learning classifiers in conjunction with novel features derived from atomistic simulations. The proposed approach is demonstrated for designing non-toxic antimicrobial peptides (AMPs) with strong broad-spectrum potency, which are emerging drug candidates for tackling antibiotic resistance. Synthesis and testing of only twenty designed sequences identified two novel and minimalist AMPs with high potency against diverse Gram-positive and Gram-negative pathogens, including one multidrug-resistant and one antibiotic-resistant K. pneumoniae, via membrane pore formation. Both antimicrobials exhibit low in vitro and in vivo toxicity and mitigate the onset of drug resistance. The proposed approach thus presents a viable path for faster and efficient discovery of potent and selective broad-spectrum antimicrobials.