From Static Structures to Ensembles: Studying and Harnessing Protein Structure Tokenization

Zijing Liu; Bin Feng; He Cao; Yu Li

Home/Archive/arXiv

arXiv · 2511.10056

From Static Structures to Ensembles: Studying and Harnessing Protein Structure Tokenization

Zijing Liu·Bin Feng·He Cao·Yu Li

View original source ↗Read source document ↗Export metadata ↓

Abstract

Protein structure tokenization converts 3D structures into discrete or vectorized representations, enabling the integration of structural and sequence data. Despite many recent works on structure tokenization, the properties of the underlying discrete representations are not well understood. In this work, we first demonstrate that the successful utilization of structural tokens in a language model for structure prediction depends on using rich, pre-trained sequence embeddings to bridge the semantic gap between the sequence and structural "language". The analysis of the structural vocabulary itself then reveals significant semantic redundancy, where multiple distinct tokens correspond to nearly identical local geometries, acting as "structural synonyms". This redundancy, rather than being a flaw, can be exploited with a simple "synonym swap" strategy to generate diverse conformational ensembles by perturbing a predicted structure with its structural synonyms. This computationally lightweight method accurately recapitulates protein flexibility, performing competitively with state-of-the-art models. Our study provides fundamental insights into the nature of discrete protein structure representations and introduces a powerful, near-instantaneous method for modeling protein dynamics. Source code is available in https://github.com/IDEA-XL/TokenMD.

Explore related subjects

cs.LG

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Zijing Liu, Bin Feng, He Cao, Yu Li. 2025-11-13. From Static Structures to Ensembles: Studying and Harnessing Protein Structure Tokenization. https://arxiv.org/abs/2511.10056

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

arXiv2026

Analysis of Regularized Learning in Banach Spaces for Linear-functional Data

This article delves into the study of the theory of regularized learning in Banach spaces for linear-functional data. It encompasses discussions on representer theorems, pseudo-approximation theorems, and convergence theorems. Regularized learning is designed to minimize regularized empirical risks over a Banach space. The empirical risks are calculated by utilizing training data and multi-loss functions. The input training data are composed of linear functionals in a predual space of the Banach space to capture discrete local information from multimodal data and multiscale models. Through the regularized learning, approximations of the exact solution to an unidentified or uncertain original problem are globally achieved. In the convergence theorems, the convergence of the approximate solutions to the exact solution is established through the utilization of the weak* topology of the Banach space. The theorems of regularized learning are utilized in the interpretation of classical machine learning, such as support vector machines and artificial neural networks.

cs.LG↗

arXiv2026

On Minimal Depth in Neural Networks

Understanding the relationship between the depth of a neural network and its representational capacity is a central problem in deep learning theory. In this work, we develop a geometric framework to analyze the expressivity of ReLU networks with the notion of depth complexity for convex polytopes. The depth of a polytope recursively quantifies the number of alternating convex hull and Minkowski sum operations required to construct it. This geometric perspective serves as a rigorous tool for deriving depth lower bounds and understanding the structural limits of deep neural architectures. We establish lower and upper bounds on the depth of polytopes, as well as tight bounds for classical families. These results yield two main consequences. First, we provide a purely geometric proof of the expressivity bound by Arora et al. (2018), confirming that $\lceil \log_2(n+1)\rceil$ hidden layers suffice to represent any continuous piecewise linear (CPWL) function. Second, we prove that, unlike general ReLU networks, convex polytopes do not admit a universal depth bound. Specifically, the depth of cyclic polytopes in dimensions $n \geq 4$ grows unboundedly with the number of vertices. This result implies that Input Convex Neural Networks (ICNNs) cannot represent all convex CPWL functions with a fixed depth, revealing a sharp separation in expressivity between ICNNs and standard ReLU networks.

cs.LG↗

arXiv2026

DeepSPoC: A Deep Learning Based Sequential Propagation of Chaos

Classical particle methods based on propagation of chaos (PoC) have been developed for solving mean-field stochastic differential equations and their associated nonlinear Fokker--Planck equations. However, direct PoC implementations are difficult to apply to high-dimensional problems because they require simulating and storing large numbers of interacting particles, often with high particle-particle interaction costs. Motivated by these limitations, we build on the recently proposed sequential propagation of chaos (SPoC) framework, which replaces the fully interacting particle system in PoC with a sequential interaction mechanism. Based on this structure, we present DeepSPoC, a neural particle method that embeds a neural density representation into the sequential particle dynamics. DeepSPoC simulates particles batch by batch, while the neural network represents the evolving empirical law and is substituted into the coefficients of the mean-field SDE, thereby replacing direct particle-particle interactions with particle-network interactions. In DeepSPoC, a recently developed normalizing flow model called KRnet is used to approximate the empirical measure of particles. Compared with direct particle implementations, DeepSPoC substantially reduces memory consumption and evaluates interaction terms more efficiently, thereby improving scalability for high-dimensional problems. We apply DeepSPoC to a wide range of mean-field equations and verify its effectiveness and computational advantages.

cs.LG↗