Backdiff: a diffusion model for generalized transferable protein backmapping (2310.01768v2)

Abstract: Coarse-grained (CG) models play a crucial role in the study of protein structures, protein thermodynamic properties, and protein conformation dynamics. Due to the information loss in the coarse-graining process, backmapping from CG to all-atom configurations is essential in many protein design and drug discovery applications when detailed atomic representations are needed for in-depth studies. Despite recent progress in data-driven backmapping approaches, devising a backmapping method that can be universally applied across various CG models and proteins remains unresolved. In this work, we propose BackDiff, a new generative model designed to achieve generalization and reliability in the protein backmapping problem. BackDiff leverages the conditional score-based diffusion model with geometric representations. Since different CG models can contain different coarse-grained sites which include selected atoms (CG atoms) and simple CG auxiliary functions of atomistic coordinates (CG auxiliary variables), we design a self-supervised training framework to adapt to different CG atoms, and constrain the diffusion sampling paths with arbitrary CG auxiliary variables as conditions. Our method facilitates end-to-end training and allows efficient sampling across different proteins and diverse CG models without the need for retraining. Comprehensive experiments over multiple popular CG models demonstrate BackDiff's superior performance to existing state-of-the-art approaches, and generalization and flexibility that these approaches cannot achieve. A pretrained BackDiff model can offer a convenient yet reliable plug-and-play solution for protein researchers, enabling them to investigate further from their own CG models.