pyDNA-EPBD is a Python-based software tool that employs an extended version of the Peyrard–Bishop–Dauxois (EPBD) model. This extension integrates a sequence-dependent stacking term, enabling a more precise description of the DNA melting behavior for homogenous and periodic sequences. Through the use of a Monte Carlo Markov Chain (MCMC) approach, pyDNA-EPBD simulates DNA dynamics and generates data on DNA breathing characteristics such as bubble coordinates and flipping.