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Antibody therapeutics has been extensively studied in drug discovery and development within the past decades. One increasingly popular focus in the antibody discovery pipeline is the optimization step for therapeutic leads. Both traditional…

Biomolecules · Quantitative Biology 2022-08-16 Yue Kang , Dawei Leng , Jinjiang Guo , Lurong Pan

Antibody lead optimization is inherently a multi-objective challenge in drug discovery. Achieving a balance between different drug-like properties is crucial for the development of viable candidates, and this search becomes exponentially…

Machine Learning · Computer Science 2026-04-16 Jackie Rao , Ferran Gonzalez Hernandez , Leon Gerard , Alexandra Gessner

We study a fundamental problem in structure-based drug design -- generating molecules that bind to specific protein binding sites. While we have witnessed the great success of deep generative models in drug design, the existing methods are…

Biomolecules · Quantitative Biology 2022-11-15 Shitong Luo , Jiaqi Guan , Jianzhu Ma , Jian Peng

Structure-based drug design (SBDD) aims to design small-molecule ligands that bind with high affinity and specificity to pre-determined protein targets. Generative SBDD methods leverage structural data of drugs in complex with their protein…

Deep generative models that learn from the distribution of natural protein sequences and structures may enable the design of new proteins with valuable functions. While the majority of today's models focus on generating either sequences or…

Biomolecules · Quantitative Biology 2024-10-03 Chentong Wang , Sarah Alamdari , Carles Domingo-Enrich , Ava Amini , Kevin K. Yang

Generative models for structure-based molecular design hold significant promise for drug discovery, with the potential to speed up the hit-to-lead development cycle, while improving the quality of drug candidates and reducing costs. Data…

Machine Learning · Statistics 2022-04-25 Lucian Chan , Rajendra Kumar , Marcel Verdonk , Carl Poelking

Protein sequence design is a challenging problem in protein engineering, which aims to discover novel proteins with useful biological functions. Directed evolution is a widely-used approach for protein sequence design, which mimics the…

Machine Learning · Computer Science 2023-03-21 Chuanjiao Zong

Structure-based drug design aims at generating high affinity ligands with prior knowledge of 3D target structures. Existing methods either use conditional generative model to learn the distribution of 3D ligands given target binding sites,…

Biomolecules · Quantitative Biology 2024-03-18 Yuwei Yang , Siqi Ouyang , Xueyu Hu , Mingyue Zheng , Hao Zhou , Lei Li

Computational protein design, i.e. inferring novel and diverse protein sequences consistent with a given structure, remains a major unsolved challenge. Recently, deep generative models that learn from sequences alone or from sequences and…

Biomolecules · Quantitative Biology 2021-11-15 Igor Melnyk , Payel Das , Vijil Chenthamarakshan , Aurelie Lozano

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…

We perform an experimental end-to-end transceiver optimization via deep learning using a generative adversarial network to approximate the test-bed channel. Previously, optimization was only possible through a prior assumption of an…

Information Theory · Computer Science 2019-12-19 Boris Karanov , Mathieu Chagnon , Vahid Aref , Domaniç Lavery , Polina Bayvel , Laurent Schmalen

Modern therapeutic antibody design often involves composing multi-part assemblages of individual functional domains, each of which may be derived from a different source or engineered independently. While these complex formats can expand…

Machine Learning · Computer Science 2025-09-25 Jiayi Xin , Aniruddh Raghu , Nick Bhattacharya , Adam Carr , Melanie Montgomery , Hunter Elliott

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

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

We propose generative neural network methods to generate DNA sequences and tune them to have desired properties. We present three approaches: creating synthetic DNA sequences using a generative adversarial network; a DNA-based variant of…

Machine Learning · Computer Science 2017-12-19 Nathan Killoran , Leo J. Lee , Andrew Delong , David Duvenaud , Brendan J. Frey

Deep learning approaches have produced substantial breakthroughs in fields such as image classification and natural language processing and are making rapid inroads in the area of protein design. Many generative models of proteins have been…

Machine Learning · Computer Science 2021-09-29 Alexey Strokach , Philip M. Kim

To build effective therapeutics, biologists iteratively mutate antibody sequences to improve binding and stability. Proposed mutations can be informed by previous measurements or by learning from large antibody databases to predict only…

Biological machine learning is often bottlenecked by a lack of scaled data. One promising route to relieving data bottlenecks is through high throughput screens, which can experimentally test the activity of $10^6-10^{12}$ protein sequences…

Machine Learning · Statistics 2025-10-21 Eli N. Weinstein , Andrei Slabodkin , Mattia G. Gollub , Elizabeth B. Wood

To fully leverage the capabilities of diffusion models, we are often interested in optimizing downstream reward functions during inference. While numerous algorithms for reward-guided generation have been recently proposed due to their…

Machine Learning · Computer Science 2025-04-18 Masatoshi Uehara , Xingyu Su , Yulai Zhao , Xiner Li , Aviv Regev , Shuiwang Ji , Sergey Levine , Tommaso Biancalani

Therapeutic antibody development has become an increasingly popular approach for drug development. To date, antibody therapeutics are largely developed using large scale experimental screens of antibody libraries containing hundreds of…

Quantitative Methods · Quantitative Biology 2022-10-07 Lin Li , Esther Gupta , John Spaeth , Leslie Shing , Tristan Bepler , Rajmonda Sulo Caceres