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Protein inverse folding-that is, predicting an amino acid sequence that will fold into the desired 3D structure-is an important problem for structure-based protein design. Machine learning based methods for inverse folding typically use…

Artificial Intelligence · Computer Science 2024-10-23 Yasha Ektefaie , Olivia Viessmann , Siddharth Narayanan , Drew Dresser , J. Mark Kim , Armen Mkrtchyan

In this work, we aim to solve data-driven optimization problems, where the goal is to find an input that maximizes an unknown score function given access to a dataset of inputs with corresponding scores. When the inputs are high-dimensional…

Machine Learning · Computer Science 2020-01-01 Aviral Kumar , Sergey Levine

Optimal design of experiments for Bayesian inverse problems has recently gained wide popularity and attracted much attention, especially in the computational science and Bayesian inversion communities. An optimal design maximizes a…

Optimization and Control · Mathematics 2023-05-09 Ahmed Attia , Sven Leyffer , Todd Munson

A reduced model, which can fold both helix and sheet structures, is proposed to study the problem of protein folding. The goal of this model is to find an unbiased effective potential that has included the effects of water and at the same…

Soft Condensed Matter · Physics 2007-05-23 Nan-yow Chen

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

Adeno-associated viral (AAV) vectors are widely used delivery platforms in gene therapy, and the design of improved capsids is key to expanding their therapeutic potential. A central challenge in AAV bioengineering, as in protein design…

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

The goal of structure-based drug discovery is to find small molecules that bind to a given target protein. Deep learning has been used to generate drug-like molecules with certain cheminformatic properties, but has not yet been applied to…

Quantitative Methods · Quantitative Biology 2022-01-27 Matthew Ragoza , Tomohide Masuda , David Ryan Koes

PDE-constrained inverse problems are some of the most challenging and computationally demanding problems in computational science today. Fine meshes that are required to accurately compute the PDE solution introduce an enormous number of…

Numerical Analysis · Mathematics 2023-04-12 Jonathan Wittmer , Jacob Badger , Hari Sundar , Tan Bui-Thanh

Designing protein sequences with optimal energetic stability is a key challenge in protein inverse folding, as current deep learning methods are primarily trained by maximizing sequence recovery rates, often neglecting the energy of the…

Machine Learning · Computer Science 2025-06-12 Dingyi Rong , Haotian Lu , Wenzhuo Zheng , Fan Zhang , Shuangjia Zheng , Ning Liu

We propose a structured prior for high-dimensional Bayesian inverse problems based on a disentangled deep generative model whose latent space is partitioned into auxiliary variables aligned with known and interpretable physical parameters…

Computation · Statistics 2026-04-03 Arkaprabha Ganguli , Emil Constantinescu

Protein folding, which dictates the protein structure from its amino acid sequence, is half a century old problem of biology. The function of the protein correlates with its structure, emphasizing the need of understanding protein folding…

Quantum Physics · Physics 2025-01-03 Jaya Vasavi P , Soham Bopardikar , Avinash D , Ashwini K , Kalyan Dasgupta , Sanjib Senapati

Protein design is the inverse approach of the three-dimensional (3D) structure prediction for elucidating the relationship between the 3D structures and amino acid sequences. In general, the computation of the protein design involves a…

Biological Physics · Physics 2021-07-14 Tomoei Takahashi , George Chikenji , Kei Tokita

Protein contacts provide key information for the understanding of protein structure and function, and therefore contact prediction from sequences is an important problem. Recent research shows that some correctly predicted long-range…

Quantitative Methods · Quantitative Biology 2020-09-02 Siqi Sun

Deep neural network approaches to inverse imaging problems have produced impressive results in the last few years. In this paper, we consider the use of generative models in a variational regularisation approach to inverse problems. The…

Image and Video Processing · Electrical Eng. & Systems 2022-06-22 Margaret Duff , Neill D. F. Campbell , Matthias J. Ehrhardt

The techniques of data-driven backmapping from coarse-grained (CG) to fine-grained (FG) representation often struggle with accuracy, unstable training, and physical realism, especially when applied to complex systems such as proteins. In…

Machine Learning · Computer Science 2025-05-26 Georgios Kementzidis , Erin Wong , John Nicholson , Ruichen Xu , Yuefan Deng

Therapeutic antibody candidates often require extensive engineering to improve key functional and developability properties before clinical development. This can be achieved through iterative design, where starting molecules are optimized…

Machine Learning · Computer Science 2025-09-23 Aniruddh Raghu , Sebastian Ober , Maxwell Kazman , Hunter Elliott

Protein sequences serve as a natural record of the evolutionary constraints that shape their functional structures. We show that it is possible to use only sequence information to go beyond predicting native structures and global stability…

Biomolecules · Quantitative Biology 2025-07-02 Ezequiel A. Galpern , Ernesto A. Roman , Diego U. Ferreiro

Automated chemical synthesis, materials fabrication, and spectroscopic physical measurements often bring forth the challenge of process trajectory optimization, i.e., discovering the time dependence of temperature, electric field, or…

Disordered Systems and Neural Networks · Physics 2022-06-28 Mani Valleti , Rama K. Vasudevan , Maxim A. Ziatdinov , Sergei V. Kalinin

A protein's function depends critically on its conformational ensemble, a collection of energy weighted structures whose balance depends on temperature and environment. Though recent deep learning (DL) methods have substantially advanced…

Biomolecules · Quantitative Biology 2026-01-09 Myeongsang Lee , Lauren L. Porter