Exploit Your Latents: Coarse-Grained Protein Backmapping with Latent Diffusion Models

Abstract

Coarse-grained (CG) molecular dynamics of proteins is a preferred approach to studying large molecules on extended time scales by condensing the entire atomic model into a limited number of pseudo-atoms and preserving the thermodynamic properties of the system. However, the significantly increased efficiency impedes the analysis of substantial physicochemical information, since high-resolution atomic details are sacrificed to accelerate simulation. In this paper, we propose LatCPB, a generative approach based on diffusion that enables high-resolution backmapping of CG proteins. Specifically, our model encodes an all-atom into discrete latent embeddings, aligned with learnable multimodal discrete priors for circumventing posterior collapse and maintaining the discrete properties of the protein sequence. During the generation, we further design a latent diffusion process within the continuous latent space due to the potential stochastics in the data. Moreover, LatCPB performs a contrastive learning strategy in latent space to separate feature representations of various molecules and conformations of the same molecule, thus enhancing the comprehension of molecular representational diversity. Experimental results demonstrate that LatCPB is able to backmap CG proteins effectively and achieve outstanding performance.