PepEVOLVE is a dynamic, position‑aware framework for optimizing macrocyclic peptides that learns where to edit and how to improve multiple properties. It enhances pretraining with dynamic masking and CHUCKLES shifting, employs a multi‑armed‑bandit router to identify high‑reward residues, and uses an evolving optimization algorithm with group‑relative advantage to stabilize updates. In in‑silico tests on a Rev‑binding macrocycle benchmark, PepEVOLVE surpassed PepINVENT, achieving higher permeability‑weighted scores and converging faster while respecting structural constraints.
arXiv:2608. 19808v1 Announce Type: new Abstract: Cyclic peptides are emerging as promising molecular scaffolds in drug discovery due to their high binding affinity and structural stability.
Cyclic peptides are emerging as promising molecular scaffolds in drug discovery due to their high binding affinity and structural stability. However, extending generative models from linear to cyclic...
arXiv:2608. 11483v1 Announce Type: new Abstract: Hit-to-lead optimization requires iterative design of hit analogs across competing potency, selectivity, physicochemical, pharmacokinetic, safety, and synthetic constraints.
arXiv:2606. 14510v1 Announce Type: new Abstract: Macrocyclic peptides are promising therapeutic candidates for intracellular targets, but their design requires simultaneous control over non-natural monomer chemistry, ring topology, membrane permeability, and target binding.
arXiv:2609.00189v1 Announce Type: new Abstract: Goal-directed optimization is essential for steering molecular generators to propose candidates with desired properties. However, it is often implement...
Pepti-drift is a one‑step peptide generation framework that uses a single latent refinement and parallel decoding, avoiding costly inference‑time guidance. It incorporates attraction toward target‑specific binders and repulsion from liability‑associated regions, achieving an 18.37% predicted Safe‑Active yield across 88 held‑out targets. The method delivers competitive gains to multi‑property‑guided baselines while reducing generation cost by 468×, enabling scalable and fair high‑throughput peptide design.
ReMedI introduces an inference‑time refinement framework that combines a pre‑trained molecular language model with a Metropolis‑Hastings search to perform multi‑objective optimization of drug leads. The method proposes edits conditioned on the current molecule and refines them to improve properties, preserve lead similarity, and maintain scaffold integrity. Experiments on C‑MuMOInstruct and SMDD benchmarks show that ReMedI outperforms RL‑based baselines, achieving higher success rates and requiring far fewer training leads.
arXiv:2607. 02834v1 Announce Type: new Abstract: Molecular optimization often starts from a pretrained generative model that captures a broad prior over valid molecular structures.
arXiv:2606. 12991v1 Announce Type: new Abstract: Cyclic peptides represent a promising class of therapeutic compounds in modern drug discovery, often offering improved stability and binding affinity.
arXiv:2606. 00555v1 Announce Type: new Abstract: Structure-based drug design increasingly employs LLM agents to iteratively refine ligands against a target pocket, yet a viable ligand must satisfy two often-conflicting objectives -- binding affinity and druggability -- which single optimization steps rarely improve together.
arXiv:2610.19920v1 Announce Type: new Abstract: Molecular design is often formulated as an optimization problem over existing molecular spaces. However, molecular optimization and the discovery of st...
Molecular design is often formulated as an optimization problem over existing molecular spaces. However, molecular optimization and the discovery of structurally distinct replacement molecules represe...