PolymerGPT: Multi-property Optimization with a Decoder-Based GPT Model for Generative Polymer Design

Polymer property prediction and inverse generative design targeting desired properties are two crucial tasks in machine learning-assisted polymer design. While the former has received considerable attention, there have been limited methods developed for the latter. Existing methods focus on single-property optimization in the generative process, whereas accurate prediction of macroscopic material behavior requires simultaneous control of multiple physical properties. In this paper, we provide a transformative framework for direct optimization of a large collection of polymer properties. We propose PolymerGPT, a decoder-based GPT model that incorporates up to 37 commonly used polymer properties into the generative process via learned conditioning prefixes. It also supports a scaffold condition that specifies a desired scaffold for predicted structures. Our experimental results demonstrate that PolymerGPT achieves exceptional performance for unconditional and conditional generation while maintaining high validity, uniqueness, and novelty. Conditioning on five key properties yields generated structures whose predicted values closely match all target properties simultaneously.

Reward Transport: Property Control in Flow Matching via Noise-Space Alignment

The coupling in flow matching -- the rule pairing noise vectors with data points -- is typically treated as a computational choice. We show that this coupling can instead serve as an alignment interface: by matching noise and data according to a target molecular property, it embeds controllable structure directly into the learned flow field. Building on this view, we introduce Reward Transport, which uses optimal transport coupling at training time to align a scalar noise-space coordinate with molecular rewards; at inference, varying this coordinate steers the generated distribution without requiring an oracle, reward model, gradient guidance, or additional computation. In the coupling-preserving limit, thresholding this coordinate recovers the Cross-Entropy Method's truncated reward distribution, providing a principled, continuously adjustable distribution-level control knob. Empirically, on ZINC-250K and GuacaMol, sweeping the scalar induces monotone control of logP and consistent QED control over its operating range; most tellingly, the same knob produces opposite structural responses for different targets, growing molecules for logP but shrinking them for QED, which rules out a generic size bias. The interface is complementary to classifier-free guidance and conditional flow matching, while a negative result under epsilon-prediction diffusion clarifies where coupling-level alignment is structurally absent. Code: https://github.com/KehanGuo2/reward-transport

APCyc: Property-Informed Design of Cyclic Peptides via Automated Cyclization

Cyclic peptides represent a promising class of therapeutic compounds in modern drug discovery, often offering improved stability and binding affinity. However, the de novo design of cyclic peptides remains challenging because methods must identify pocket-adaptive cyclization patterns and linkage sites while simultaneously controlling drug-relevant properties. This challenge is particularly pronounced for recent generative models trained predominantly on linear peptide data, which may fail to capture cyclization-specific constraints. To address the limitation, we introduce APCyc, a target-aware de novo cyclic peptide generation framework that explicitly models cyclization and jointly optimizes multiple essential physicochemical properties. By using an expanded residue vocabulary and explicitly encoding cyclization-site and linkage-type information, APCyc learns cyclization-aware representations and leverages Bayesian posterior guidance to steer sampling toward cyclic peptides satisfying multiple property objectives. Experimental results demonstrate that our model learns target-dependent cyclization preferences, and enables effective and controllable multi-property optimization for cyclic peptide design. The source code of this paper is available at https://github.com/HKUSTGZ-ML4Health-Lab/APCyc.