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Through evolution, nature has presented a set of remarkable protein materials, including elastins, silks, keratins and collagens with superior mechanical performances that play crucial roles in mechanobiology. However, going beyond natural…

Materials Science · Physics 2023-12-19 Bo Ni , David L. Kaplan , Markus J. Buehler

We review algorithms for protein design in general. Although these algorithms have a rich combinatorial, geometric, and mathematical structure, they are almost never covered in computer science classes. Furthermore, many of these algorithms…

Computational Engineering, Finance, and Science · Computer Science 2019-10-01 Mark A. Hallen , Bruce R. Donald

Deep learning is catalyzing a scientific revolution fueled by big data, accessible toolkits, and powerful computational resources, impacting many fields including protein structural modeling. Protein structural modeling, such as predicting…

Biomolecules · Quantitative Biology 2020-07-17 Wenhao Gao , Sai Pooja Mahajan , Jeremias Sulam , Jeffrey J. Gray

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

Designing de novo proteins beyond those found in nature holds significant promise for advancements in both scientific and engineering applications. Current methodologies for protein design often rely on AI-based models, such as surrogate…

Soft Condensed Matter · Physics 2024-02-08 A. Ghafarollahi , M. J. Buehler

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

Recent advancements in specialized large-scale architectures for training image and language have profoundly impacted the field of computer vision and natural language processing (NLP). Language models, such as the recent ChatGPT and GPT4…

Biomolecules · Quantitative Biology 2023-05-04 Sergio Romero-Romero , Sebastian Lindner , Noelia Ferruz

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…

The de novo design of molecular structures using deep learning generative models introduces an encouraging solution to drug discovery in the face of the continuously increased cost of new drug development. From the generation of original…

Biomolecules · Quantitative Biology 2021-02-08 Yuemin Bian , Xiang-Qun Xie

Deep learning in \emph{de novo} protein design has achieved atomic-level fidelity. However, existing models remain largely non-deliberative: they directly synthesize molecular geometries without explicitly reasoning about which residues or…

Proteins are macromolecules that mediate a significant fraction of the cellular processes that underlie life. An important task in bioengineering is designing proteins with specific 3D structures and chemical properties which enable…

Quantitative Methods · Quantitative Biology 2022-05-31 Namrata Anand , Tudor Achim

The discovery of functional molecules is an expensive and time-consuming process, exemplified by the rising costs of small molecule therapeutic discovery. One class of techniques of growing interest for early-stage drug discovery is de novo…

Quantitative Methods · Quantitative Biology 2020-02-18 Wenhao Gao , Connor W. Coley

Generative modeling for protein engineering is key to solving fundamental problems in synthetic biology, medicine, and material science. We pose protein engineering as an unsupervised sequence generation problem in order to leverage the…

The recent surge in Generative Artificial Intelligence (AI) has introduced exciting possibilities for computational chemistry. Generative AI methods have made significant progress in sampling molecular structures across chemical species,…

Statistical Mechanics · Physics 2024-09-06 Pratyush Tiwary , Lukas Herron , Richard John , Suemin Lee , Disha Sanwal , Ruiyu Wang

"How to evaluate the de novo designs proposed by a generative model?" Despite the transformative potential of generative deep learning in drug discovery, this seemingly simple question has no clear answer. The absence of standardized…

Biomolecules · Quantitative Biology 2025-11-14 Rıza Özçelik , Francesca Grisoni

De novo design seeks to generate molecules with required property profiles by virtual design-make-test cycles. With the emergence of deep learning and neural generative models in many application areas, models for molecular design based on…

Quantitative Methods · Quantitative Biology 2021-01-05 Nathan Brown , Marco Fiscato , Marwin H. S. Segler , Alain C. Vaucher

The design of molecules and materials with tailored properties is challenging, as candidate molecules must satisfy multiple competing requirements that are often difficult to measure or compute. While molecular structures, produced through…

Chemical Physics · Physics 2023-02-07 Julia Westermayr , Joe Gilkes , Rhyan Barrett , Reinhard J. Maurer

Machine learning-based design has gained traction in the sciences, most notably in the design of small molecules, materials, and proteins, with societal implications spanning drug development and manufacturing, plastic degradation, and…

Machine Learning · Computer Science 2025-04-04 Clara Fannjiang , Jennifer Listgarten

The integration of artificial intelligence (AI) in early-stage drug discovery offers unprecedented opportunities for exploring chemical space and accelerating hit-to-lead optimization. However, docking optimization in generative approaches…

Quantitative Methods · Quantitative Biology 2025-10-03 Ekaterina Podplutova , Anastasia Vepreva , Olga A. Konovalova , Vladimir Vinogradov , Dmitrii O. Shkil , Andrei Dmitrenko

De novo molecular design has facilitated the exploration of large chemical space to accelerate drug discovery. Structure-based de novo method can overcome the data scarcity of active ligands by incorporating drug-target interaction into…

Biomolecules · Quantitative Biology 2022-09-16 Yaqin Li , Lingli Li , Yongjin Xu , Yi Yu