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We consider the protein sequence engineering problem, which aims to find protein sequences with high fitness levels, starting from a given wild-type sequence. Directed evolution has been a dominating paradigm in this field which has an…

Machine Learning · Computer Science 2025-01-20 Yinkai Wang , Jiaxing He , Yuanqi Du , Xiaohui Chen , Jianan Canal Li , Li-Ping Liu , Xiaolin Xu , Soha Hassoun

Generative image modeling techniques such as GAN demonstrate highly convincing image generation result. However, user interaction is often necessary to obtain the desired results. Existing attempts add interactivity but require either…

Graphics · Computer Science 2020-09-01 Toby Chong Long Hin , I-Chao Shen , Issei Sato , Takeo Igarashi

Protein design is a fundamental challenge in biotechnology, aiming to design novel sequences with specific functions within the vast space of possible proteins. Recent advances in deep generative models have enabled function-based protein…

Machine Learning · Computer Science 2025-10-15 Nuowei Liu , Jiahao Kuang , Yanting Liu , Tao Ji , Changzhi Sun , Man Lan , Yuanbin Wu

Reinforcement learning (RL), particularly GRPO, improves image generation quality significantly by comparing the relative performance of images generated within the same group. However, in the later stages of training, the model tends to…

Computer Vision and Pattern Recognition · Computer Science 2025-12-29 Henglin Liu , Huijuan Huang , Jing Wang , Chang Liu , Xiu Li , Xiangyang Ji

Latent-space Bayesian optimization (LSBO) extends Bayesian optimization to structured domains, such as molecular design, by searching in the continuous latent space of a generative model. However, most LSBO methods assume a fixed objective,…

Machine Learning · Statistics 2026-03-03 Tuan A. Vu , Julien Martinelli , Harri Lähdesmäki

Optimization problems find widespread use in both single-objective and multi-objective scenarios. In practical applications, users aspire for solutions that converge to the region of interest (ROI) along the Pareto front (PF). While the…

Artificial Intelligence · Computer Science 2025-03-10 Tian Huang , Shengbo Wang , Ke Li

Evolutionary algorithms, inspired by natural evolution, aim to optimize difficult objective functions without computing derivatives. Here we detail the relationship between population genetics and evolutionary optimization and formulate a…

Populations and Evolution · Quantitative Biology 2023-07-19 Jakub Otwinowski , Colin LaMont

We propose and discuss a novel strategy for protein design. The method is based on recent theoretical advancements which showed the importance to treat carefully the conformational free energy of designed sequences. In this work we show how…

Statistical Mechanics · Physics 2009-10-31 A. Rossi , A. Maritan , C. Micheletti

Proteins perform critical processes in all living systems: converting solar energy into chemical energy, replicating DNA, as the basis of highly performant materials, sensing and much more. While an incredible range of functionality has…

Biomolecules · Quantitative Biology 2021-09-29 Leonardo V. Castorina , Rokas Petrenas , Kartic Subr , Christopher W. Wood

Directed evolution of proteins has been the most effective method for protein engineering. However, a new paradigm is emerging, fusing the library generation and screening approaches of traditional directed evolution with computation…

Biomolecules · Quantitative Biology 2023-05-29 Kadina E. Johnston , Clara Fannjiang , Bruce J. Wittmann , Brian L. Hie , Kevin K. Yang , Zachary Wu

Motivation. Protein design aims to identify sequences compatible with a given protein fold but incompatible to any alternative folds. To select the correct sequences and to guide the search process, a design scoring function is critically…

Biomolecules · Quantitative Biology 2007-05-23 Changyu Hu , Xiang Li , Jie Liang

Since DeepSeek-R1 popularized, Group Relative Policy Optimization (GRPO) has become the core part of training Reasoning LLMs. However, we find some deficiency that influences RL stability and inference efficiency, like zero-variance in…

Computation and Language · Computer Science 2025-09-30 Chen Li , Nazhou Liu , Kai Yang

Fine-tuning pre-trained generative models with Reinforcement Learning (RL) has emerged as an effective approach for aligning outputs more closely with nuanced human preferences. In this paper, we investigate the application of Group…

Computer Vision and Pattern Recognition · Computer Science 2025-07-01 Matteo Gallici , Haitz Sáez de Ocáriz Borde

Volatility is a key variable in option pricing, trading and hedging strategies. The purpose of this paper is to improve the accuracy of forecasting implied volatility using an extension of genetic programming (GP) by means of dynamic…

General Finance · Quantitative Finance 2020-07-15 Sana Ben Hamida , Wafa Abdelmalek , Fathi Abid

Designing novel proteins with desired characteristics remains a significant challenge due to the large sequence space and the complexity of sequence-function relationships. Efficient exploration of this space to identify sequences that meet…

Machine Learning · Computer Science 2026-03-04 Erik Hartman , Di Tang , Johan Malmström

Most reinforcement learning algorithms seek a single optimal strategy that solves a given task. However, it can often be valuable to learn a diverse set of solutions, for instance, to make an agent's interaction with users more engaging, or…

Machine Learning · Computer Science 2024-01-09 Wentse Chen , Shiyu Huang , Yuan Chiang , Tim Pearce , Wei-Wei Tu , Ting Chen , Jun Zhu

Post-training of language models, either through reinforcement learning, preference optimization or supervised finetuning, tends to sharpen the output probability distribution and reduce the diversity of generated responses. This is…

Computation and Language · Computer Science 2025-05-23 Jack Lanchantin , Angelica Chen , Shehzaad Dhuliawala , Ping Yu , Jason Weston , Sainbayar Sukhbaatar , Ilia Kulikov

In this paper, we introduce a novel approach to multi-modal optimization by enhancing the recently developed kinetic-based optimization (KBO) method with genetic dynamics (GKBO). The proposed method targets objective functions with multiple…

Numerical Analysis · Mathematics 2024-11-12 Federica Ferrarese , Claudia Totzeck

Proteins are dynamic molecular machines whose biological functions, spanning enzymatic catalysis, signal transduction, and structural adaptation, are intrinsically linked to their motions. Designing proteins with targeted dynamic…

Biomolecules · Quantitative Biology 2025-02-17 Bo Ni , Markus J. Buehler

Molecular Dynamics (MD) simulations provide a fundamental tool for characterizing molecular behavior at full atomic resolution, but their applicability is severely constrained by the computational cost. To address this, a surge of deep…

Machine Learning · Computer Science 2026-03-02 Ziyang Yu , Wenbing Huang , Yang Liu
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