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Directed evolution is an iterative laboratory process of designing proteins with improved function by iteratively synthesizing new protein variants and evaluating their desired property with expensive and time-consuming biochemical…

Machine Learning · Computer Science 2025-09-08 Matouš Soldát , Jiří Kléma

Directed evolution is a versatile technique in protein engineering that mimics the process of natural selection by iteratively alternating between mutagenesis and screening in order to search for sequences that optimize a given property of…

Biomolecules · Quantitative Biology 2024-05-02 Lixue Cheng , Ziyi Yang , Changyu Hsieh , Benben Liao , Shengyu Zhang

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

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

Bayesian optimization (BO) is an approach to globally optimizing black-box objective functions that are expensive to evaluate. BO-powered experimental design has found wide application in materials science, chemistry, experimental physics,…

Machine Learning · Computer Science 2023-10-10 Mimi Zhang , Andrew Parnell , Dermot Brabazon , Alessio Benavoli

In many high-throughput experimental design settings, such as those common in biochemical engineering, batched queries are more cost effective than one-by-one sequential queries. Furthermore, it is often not possible to directly choose…

Machine Learning · Computer Science 2019-04-18 Kevin K. Yang , Yuxin Chen , Alycia Lee , Yisong Yue

To reduce experimental effort associated with directed protein evolution and to explore the sequence space encoded by mutating multiple positions simultaneously, we incorporate machine learning in the directed evolution workflow.…

Biomolecules · Quantitative Biology 2020-01-07 Zachary Wu , S. B. Jennifer Kan , Russell D. Lewis , Bruce J. Wittmann , Frances H. Arnold

While modern biotechnologies allow synthesizing new proteins and function measurements at scale, efficiently exploring a protein sequence space and engineering it remains a daunting task due to the vast sequence space of any given protein.…

Biomolecules · Quantitative Biology 2024-01-15 Jiahao Qiu , Hui Yuan , Jinghong Zhang , Wentao Chen , Huazheng Wang , Mengdi Wang

The design of novel protein sequences with targeted functionalities underpins a central theme in protein engineering, impacting diverse fields such as drug discovery and enzymatic engineering. However, navigating this vast combinatorial…

Biomolecules · Quantitative Biology 2024-02-19 Yiheng Zhu , Zitai Kong , Jialu Wu , Weize Liu , Yuqiang Han , Mingze Yin , Hongxia Xu , Chang-Yu Hsieh , Tingjun Hou

This paper presents a method called sampling-computation-optimization (SCO) to design batch Bayesian optimization. SCO does not construct new high-dimensional acquisition functions but samples from the existing one-site acquisition function…

Optimization and Control · Mathematics 2022-02-22 Kai Jia , Xiaojun Duan , Zhengming Wang , Liang Yan

A long-standing goal of machine-learning-based protein engineering is to accelerate the discovery of novel mutations that improve the function of a known protein. We introduce a sampling framework for evolving proteins in silico that…

Machine Learning · Computer Science 2023-04-10 Patrick Emami , Aidan Perreault , Jeffrey Law , David Biagioni , Peter C. St. John

We propose to use Bayesian optimization (BO) to improve the efficiency of the design selection process in clinical trials. BO is a method to optimize expensive black-box functions, by using a regression as a surrogate to guide the search.…

Methodology · Statistics 2021-05-20 Jakob Richter , Tim Friede , Jörg Rahnenführer

A popular approach to protein design is to combine a generative model with a discriminative model for conditional sampling. The generative model samples plausible sequences while the discriminative model guides a search for sequences with…

The ability to accelerate the design of biological sequences can have a substantial impact on the progress of the medical field. The problem can be framed as a global optimization problem where the objective is an expensive black-box…

Machine Learning · Computer Science 2022-09-15 Leo Feng , Padideh Nouri , Aneri Muni , Yoshua Bengio , Pierre-Luc Bacon

Bayesian optimization (BO) algorithms try to optimize an unknown function that is expensive to evaluate using minimum number of evaluations/experiments. Most of the proposed algorithms in BO are sequential, where only one experiment is…

Machine Learning · Computer Science 2011-10-18 Javad Azimi , Ali Jalali , Xiaoli Fern

Protein sequence design methods have demonstrated strong performance in sequence generation for de novo protein design. However, as the training objective was sequence recovery, it does not guarantee designability--the likelihood that a…

Machine Learning · Computer Science 2025-06-03 Fanglei Xue , Andrew Kubaney , Zhichun Guo , Joseph K. Min , Ge Liu , Yi Yang , David Baker

Bayesian optimization (BO) provides a powerful framework for optimizing black-box, expensive-to-evaluate functions. It is therefore an attractive tool for engineering design problems, typically involving multiple objectives. Thanks to the…

Machine Learning · Computer Science 2024-09-06 Navid Ansari , Alireza Javanmardi , Eyke Hüllermeier , Hans-Peter Seidel , Vahid Babaei

Protein engineering seeks to identify protein sequences with optimized properties. When guided by machine learning, protein sequence generation methods can draw on prior knowledge and experimental efforts to improve this process. In this…

Quantitative Methods · Quantitative Biology 2021-05-28 Zachary Wu , Kadina E. Johnston , Frances H. Arnold , Kevin K. Yang

Batched Bayesian optimization (BO) can accelerate molecular design by efficiently identifying top-performing compounds from a large chemical library. Existing acquisition strategies for batch design in BO aim to balance exploration and…

A new method for sequence optimization in protein models is presented. The approach, which has inherited its basic philosophy from recent work by Deutsch and Kurosky [Phys. Rev. Lett. 76, 323 (1996)] by maximizing conditional probabilities…

Soft Condensed Matter · Physics 2009-10-30 Anders Irbäck , Carsten Peterson , Frank Potthast , Erik Sandelin
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