Fleishman Lab

Laboratory of Protein Design

Research

Proteins are responsible for all the molecular processes that are essential to life on Earth. Our lab's mission is to understand how proteins carry out their exquisite molecular functions, such as neutralising viruses, breaking down toxic compounds, and synthesising beneficial ones. But proteins are the most complex molecules we know, each comprising hundreds of amino acids that form a unique and intricate three-dimensional structure. To solve this immense problem we develop an interdisciplinary computational and experimental strategy.

Our research combines computational methods development, including atomistic modeling and AI, and structural and biochemical wet-lab work. We probe our understanding of protein design principles by designing new proteins and testing their activities in the lab. We are committed to making methods accessible to all scientists, and our algorithms have enabled us and researchers from around the world to design antibodies, vaccines, therapeutic enzymes, and enzymes for green chemistry. We are excited to see protein design enabling the next wave of discovery in basic and applied biomolecular research.

Research page

Selected Publications

Computational optimization of antibody humanness and stability by systematic energy-based ranking

Tennenhouse A., Khmelnitsky L., Khalaila R., Yeshaya N., Noronha A., Lindzen M., Makowski E. K., Zaretsky I., Sirkis Y. F., Galon-Wolfenson Y., Tessier P. M., Abramson J., Yarden Y., Fass D. & Fleishman S. J. (2024) Nature Biomedical Engineering. 8, 1, p. 30-44

Designed active-site library reveals thousands of functional GFP variants

Weinstein J. Y., Martí-Gómez C., Lipsh-Sokolik R., Hoch S. Y., Liebermann D., Nevo R., Weissman H., Petrovich-Kopitman E., Margulies D., Ivankov D., McCandlish D. M. & Fleishman S. J. (2023) Nature Communications. 14, 2890.

Combinatorial assembly and design of enzymes

Lipsh-Sokolik R., Khersonsky O., Schröder S. P., de Boer C., Hoch S., Davies G. J., Overkleeft H. S. & Fleishman S. J. (2023) Science. 379, 6628, p. 195-201

De novo-designed transmembrane domains tune engineered receptor functions

Elazar A., Chandler N. J., Davey A. S., Weinstein J. Y., Nguyen J. V., Trenker R., Cross R. S., Jenkins M. R., Call M. J., Call M. E. & Fleishman S. J. (2022) eLife. 11, e75660.

Stable and Functionally Diverse Versatile Peroxidases Designed Directly from Sequences

Barber-Zucker S., Mindel V., Garcia-Ruiz E., Weinstein J. J., Alcalde M. & Fleishman S. J. (2022) Journal of the American Chemical Society. 144, 8, p. 3564-3571

Automated Design of Efficient and Functionally Diverse Enzyme Repertoires

Khersonsky O., Lipsh R., Avizemer Z., Ashani Y., Goldsmith M., Leader H., Dym O., Rogotner S., Trudeau D. L., Prilusky J., Amengual-Rigo P., Guallar V., Tawfik D. S. & Fleishman S. J. (2018) Molecular Cell. 72, 1, p. 178-186.e5

One-step design of a stable variant of the malaria invasion protein RH5 for use as a vaccine immunogen

Campeotto I., Goldenzweig A., Davey J., Barfod L., Marshall J. M., Silk S. E., Wright K. E., Draper S. J., Higgins M. K. & Fleishman S. J. (2017) Proceedings of the National Academy of Sciences of the United States of America. 114, 5, p. 998-1002

Automated Structure- and Sequence-Based Design of Proteins for High Bacterial Expression and Stability

Goldenzweig A., Goldsmith M., Hill S. E., Gertman O., Laurino P., Ashani Y., Dym O., Unger T., Albeck S., Prilusky J., Lieberman R. L., Aharoni A., Silman I., Sussman J., Tawfik D. & Fleishman S. J. (2016) Molecular Cell. 63, 2, p. 337-346
All Publications