AMPGAN v2: Machine Learning-Guided Design of Antimicrobial Peptides.
Journal:
Journal of chemical information and modeling
Published Date:
May 24, 2021
Abstract
Antibiotic resistance is a critical public health problem. Each year ∼2.8 million resistant infections lead to more than 35 000 deaths in the U.S. alone. Antimicrobial peptides (AMPs) show promise in treating resistant infections. However, applications of known AMPs have encountered issues in development, production, and shelf-life. To drive the development of AMP-based treatments, it is necessary to create design approaches with higher precision and selectivity toward resistant targets. Previously, we developed AMPGAN and obtained proof-of-concept evidence for the generative approach to design AMPs with experimental validation. Building on the success of AMPGAN, we present AMPGAN v2, a bidirectional conditional generative adversarial network (BiCGAN)-based approach for rational AMP design. AMPGAN v2 uses generator-discriminator dynamics to learn data-driven priors and controls generation using conditioning variables. The bidirectional component, implemented using a learned encoder to map data samples into the latent space of the generator, aids iterative manipulation of candidate peptides. These elements allow AMPGAN v2 to generate candidates that are novel, diverse, and tailored for specific applications, making it an efficient AMP design tool.