Publications - Arnold Group Skip to content Arnold Group Research Research Overview Methods in Protein Engineering Archived Projects Members Frances H Arnold Current Members Alumni Publications Other Awards Patents Software Protein Structures Photos Photos from Nobel Ceremony Archives Awards News Archive Press Releases Publications 2026 “Machine Learning-Assisted Evolution of Broadly Functional Enzyme Libraries.” R. G. Lal, J. Yang, Z. Zhang, and F. H. Arnold. bioRxiv., July 24, 2026. https://doi.org/10.64898/2026.07.23.740427 “Engineering Enantiocomplementary Protoglobins for Stereoconvergent Construction of N-Alkylated α-Aminoketones.” Z.Y. Qin, Z.Q. Li, C. Zhang, J.L. Heise, R. Mao, S.J. Wu, K. N. Houk, W. A. Goddard, and F. H. Arnold. J. Am. Chem. Soc., May 1, 2026. https://doi.org/10.1021/jacs.5c17989 “Conditioning protein language models using high-throughput sequence-fitness data collection.” S.C. Yuan, J. Yang, J. Li, B. Vogeli, S.R. Krarup, E. Roberts, B. Erichsen, V.H. Mujica, K. Jijakli, S. Karst, L. Yang, A.T. Nielsen, T. Korman, & F.H. Arnold. Proceedings of the GEM Workshop at the International Conference on Learning Representations (ICLR) , April 27, 2026. https://openreview.net/pdf?id=R7bguD4XaN “General Multimodal Protein Design Enables DNA-Encoding of Chemistry.” J. Rector-Brooks, T. Lambert, M. Skreta, D. Roth, Y. Long, Z.Q. Li, X. Zhang, M. Cretu, F-Z. Li, T. Ganapathy, E. Jin, A. J. Bose, J. Yang, K. Neklyudov, Y. Bengio, A. Tong, F. H. Arnold, C.H. Liu. arXiv, April 6, 2026. https://doi.org/10.48550/arXiv.2604.05181 . Blog: https://disco-design.github.io/. Code: https://github.com/DISCO-design/DISCO. “A Chemoselective and Stereodivergent Platform of Heme-Nitrene Transferases to Access Chiral Aryl-β-Amino Esters and An Investigation of the Sequence-Activity Landscape.” J.C. Reisenbauer, H.M. Carder, A. Mora, A. Jarmamillo, and F. H. Arnold. Angew. Chem. Int. Ed., February 17, 2026. https://doi.org/10.1002/anie.202525505. “OXtal: An All-Atom Diffusion Model for Organic Crystal Structure Prediction.” E. Jin, A. C. Nica, M. Galkin, J. Rector-Brooks, K. L. K. Lee, S. Miret, F. H. Arnold, M. Bronstein, A. J. Bose, A. Tong, and C.-H. Liu. ICLR, 2026. https://doi.org/10.48550/arXiv.2512.06987. “Sequence-based generative AI design of versatile tryptophan synthases” T. Lambert, A. Tavakoli, G. Dharuman, J. Yang, V. Bhethanabotla, S. Kaur, M. Hill, A. Ramanathan, A. Anandkumar, F.H. Arnold. Nature Communications, Jan 14, 2026. https://doi.org/10.1038/s41467-026-68384-6 . “Controllable All-Atom Protein Generation with Latent Diffusion” A.X. Lu, J. Yang, Y. Long, T. Lambert, W. Yan, S.A. Robinson, K.K. Yang, V. Gligorjevic, K. Cho, R. Bonneau, N. C. Frey, F.H. Arnold, R. Abbeel. bioRxiv, Jan 7, 2026. https://doi.org/10.1101/2024.12.02.626353 . 2025 “A Biocatalytic Platform for the Synthesis of Organofunctional Silanes and Siloxanes.” Z. Zhang, T.J. Fulton, R.R. Maar, J.M. Roberts, D.E. Katsoulis, and F.H. Arnold. Angew. Chem. Int. Ed., Dec 26, 2025. https://doi.org/10.1002/anie.202522762. “Steering generative models with experimental data for protein fitness optimization.” J. Yang, W. Chu, D. P. Khalil, R. Astudillo, B. J. Wittmann, F. H. Arnold, and Y. Yue. NeurIPS, Dec 2025. https://doi.org/10.48550/arXiv.2505.15093. “Evaluation of machine learning-assisted directed evolution across diverse combinatorial landscapes.” F.-Z. Li, J. Yang, K. E. Johnston, E. Cursoy, Y. Yue, and F. H. Arnold. Cell Systems, September 17, 2025. https://doi.org/10.1016/j.cels.2025.101387. “Illuminating the universe of enzyme catalysis in the era of artificial intelligence.” J. Yang, F.-Z. Li, Y. Long, and F. H. Arnold. Cell Systems, August 26, 2025. https://doi.org/10.1016/j.cels.2025.101372. “Enzymatic stereodivergent synthesis of azaspiro[2.y]alkanes.” J. L. Kennemur, Y. Long ,C. J. Ko, A. Das, and F. H. Arnold. J. Am. Chem. Soc., July 22, 2025. https://doi.org/10.1021/jacs.5c07015. “Substrate-aware zero-shot predictors for non-native enzyme activities.” F.-Z. Li, L. A. Radtke, K. E. Johnston, C.-H. Liu, Y. Yue, and F. H. Arnold. GEM Workshop, ICLR, 2025. (Presented at GEM workshop, ICLR 2025, Singapore). “Priestley Medal Address 2025: A random (mostly) uphill walk” F. H. Arnold. Chem. Eng. News. March 23, 2025. (Presented at ACS Spring 2025, San Diego, CA). “Active learning-assisted directed evolution” J. Yang, R. G. Lal, J. C. Bowden, R. Astudillo, M. A. Hameedi, S. Kaur, M. Hill, Y. Yue, and F. H. Arnold. Nat. Commun. January 16, 2025. 10.1038/s41467-025-55987-8. 2024 “LevSeq: Rapid Generation of Sequence-Function Data for Directed Evolution and Machine Learning” Y. Long, A. Mora, F.-Z. Li, E. Gürsoy, K. E. Johnston, and F. H. Arnold. ACS Synth. Biol. December 24, 2024. 10.1021/acssynbio.4c00625. “Catalyzing the future: recent advances in chemical synthesis using enzymes” J. C. Reisenbauer, K. M. Sicinski, and F. H. Arnold. Curr. Opin. Chem. Biol. October 5, 2024. 10.1016/j.cbpa.2024.102536. “Biocatalytic Synthesis of α-Amino Esters via Nitrene C–H Insertion” E. Alfonzo, D. Hanley, Z.-Q. Li, K. M. Sicinski, S. Gao, and F. H. Arnold. J. Am. Chem. Soc. September 27, 2024. 10.1021/jacs.4c09989. “A combinatorially complete epistatic fitness landscape in an enzyme active site” K. E. Johnston, P. J. Almhjell, E. J. Watkins-Dulaney, G. Liu, N. J. Porter, J. Yang, and F. H. Arnold. PNAS. July 29, 2024. 10.1073/pnas.2400439121. “Reaction Discovery Using Spectroscopic Insights from an Enzymatic C–H Amination Intermediate” A. Das, S. Gao, R. G. Lal, M. H. Hicks, P. H. Oyala, and F. H. Arnold. J. Am. Chem. Soc. July 22, 2024. 10.1021/jacs.4c05761. “Stereospecific Enzymatic Conversion of Boronic Acids to Amines” D. Hanley, Z.-Q. Li, S. Gao, S. C. Virgil, F. H. Arnold, and E. Alfonzo. J. Am. Chem. Soc. July 3, 2024. . “CARE: a Benchmark Suite for the Classification and Retrieval of Enzymes” J. Yang, A. Mora, S. Liu, B. J. Wittmann, A. Anandkumar, F. H. Arnold, and Y. Yue. aRxiv. June 21, 2024. 2406.15669. “The β-subunit of tryptophan synthase is a latent tyrosine synthase” P. J. Almhjell, K. E. Johnston, N. J. Porter, J. L. Kennemur, V. C. Bhethanabotla, J. Ducharme, and F. H. Arnold. Nat. Chem. Biol. May 14, 2024. 10.1038/s41589-024-01619-z. “Biocatalytic, enantioenriched primary amination of tertiary C–H bonds” R. Mao, S. Gao, Z.-Y. Qin, T. Rogge, S. J. Wu, Z.-Q. Li, A. Das, K. N. Houk, and F. H. Arnold. Nat. Catal. May 3, 2024. 10.1038/s41929-024-01149-w. “Opportunities and Challenges for Machine Learning-Assisted Enzyme Engineering” J. Yang, F.-Z. Li, and F. H. Arnold. ACS Cent. Sci. February 5, 2024. 10.1021/acscentsci.3c01275. “Breeding Better Enzymes” F. H. Arnold. Am. Sci. January – February 2024. https://www.americanscientist.org/article/breeding-better-enzymes. “Directed evolution of enzymatic silicon-carbon bond cleavage in siloxanes” N. S. Sarai, T. J. Fulton, R. L. O’Meara, K. E. Johnston, S. Brinkmann-Chen, R. R. Maar, R. E. Tecklenburg, J. M. Roberts, J. C. T. Reddel, D. E. Katsoulis, and F. H. Arnold. Science. January 25, 2024. 10.1126/science.adi5554. “Iron Heme Enzyme-Catalyzed Cyclopropanations with Diazirines as Carbene Precursors: Computational Explorations of Diazirine Activation and Cyclopropanation Mechanism” T. Rogge, Q. Zhou, N. J. Porter, F. H. Arnold, and K. N. Houk. J. Am. Chem. Soc. January 25, 2024. 10.1021/jacs.3c06030. “An engineered enzyme that enables the stereoconvergent alkylation of alkene mixtures” R. Mao, and F. H. Arnold. Nat. Synth. January 2, 2024. 10.1038/s44160-023-00446-9. “Enzymatic Assembly of Diverse Lactone Structures: An Intramolecular C–H Functionalization Strategy” D. J. Wackelin, R. Mao, K. M. Sicinski, Y. Zhao, A. Das, K. Chen, and F. H. Arnold. J. Am. Chem. Soc. January 2, 2024. 10.1021/jacs.3c11722. 2023 “Expanding Biocatalysis for Organosilane Functionalization: Enantioselective Nitrene Transfer to Benzylic Si–C–H Bonds” A. Das, Y. Long, R. R. Maar, J. M. Roberts, and F. H. Arnold. ACS Catal. December 16, 2023. 10.1021/acscatal.3c05370. “Biocatalytic Construction of Chiral Pyrrolidines and Indolines via Intramolecular C(sp3)–H Amination” Z-Y. Qin, S. Gao, Y. Zou, Z. Liu, J. B. Wang, K. N. Houk, and F. H. Arnold. ACS Cent. Sci. December 14, 2023. 10.1021/acscentsci.3c00516. “Biocatalytic, stereoconvergent alkylation of (Z/E)-trisubstituted silyl enol ethers” R. Mao, D. M. Taylor, D. J. Wackelin, T. Rogge, S. J. Wu, K. M. Sicinski, K. N. Houk, and F. H. Arnold. Nat. Synth. November 2, 2023. 10.1038/s44160-023-00431-2. “Directed evolution for Si–C bond cleavage of volatile siloxanes in glass bioreactors” T. J. Fulton, N. S. Sarai, R. L. O’Meara, F. H. Arnold. Methods Enzymol. October 19, 2023. 10.1016/bs.mie.2023.09.014. “Directed evolution of P411 enzymes for amination of inert C–H bonds” A. Das, S. Gao, S. V. Athavale, E. Alfonzo, Y. Long, and F. H Arnold. Methods Enzymol. October 13, 2023. 10.1016/bs.mie.2023.09.009. “Enzymatic Nitrogen Incorporation Using Hydroxylamine” S. Gao, A. Das, E. Alfonzo, K. M. Sicinski, D. Rieger, and F. H. Arnold. J. Am. Chem. Soc. September 6, 2023. 10.1021/jacs.3c08053. “DeCOIL: Optimization of Degenerate Codon Libraries for Machine Learning-Assisted Protein Engineering” J. Yang, J. Ducharme, KE. Johnston, FZ. Li, Y. Yue, and F. H. Arnold. ACS Synth. Biol. July 31, 2023. 10.1021/acssynbio.3c00301. “Enantio- and Diastereoenriched Enzymatic Synthesis of 1,2,3-Polysubstituted Cyclopropanes from (Z/E)-Trisubstituted Enol Acetates” R. Mao, D. J. Wackelin, C. S. Jamieson, T. Rogge, S. Gao, A. Das, D. M. Taylor, K. N. Houk, and F. H. Arnold. J. Am. Chem. Soc. July 11, 2023. 10.1021/jacs.3c04870. “Reversing the Enantioselectivity of Enzymatic Carbene N−H Insertion Through Mechanism-Guided Protein Engineering” C. Calvó-Tusell, Z. Liu, K. Chen, F. H. Arnold, and M. Garcia-Borràs. Angew. Chem. Int. Ed. June 01, 2023. 10.1002/anie.202303879. “Machine Learning for Protein Engineering” K. E. Johnston, C. Fannjiang, B. J. Wittmann, B. L. Hie, K. K. Yang, Z. Wu. arXiv. May 26, 2023. arXiv:2305.16634v1 . “MicroED Structure of a Protoglobin Reactive Carbene Intermediate” E. Danelius, N. J. Porter, J. Unge, F. H. Arnold, and T. Gonen. J. Am. Chem. Soc. March 22, 2023. 10.1021/jacs.2c12004. “Chemodivergent C(sp3)–H and C(sp2)–H cyanomethylation using engineered carbene transferases” J. Zhang, A. O. Maggiolo, E. Alfonzo, R. Mao, N. J. Porter, N. M. Abney, and F. H. Arnold. Nat. Catal. January 19, 2023. 10.1038/s41929-022-00908-x. “Creating New Enzymes with Evolution” P. Almhjell and F. H. Arnold. Veloxsci. 2023. 10.60150/0XIM8S. 2022 “Protoglobin-catalyzed formation of cis-trifluoromethyl-substituted cyclopropanes via carbene transfer.” L. Schaus, A. Das, A. M. Knight, G. Jimenez-Osés, K. N. Houk, M. Garcia-Borràs, F. H. Arnold, X. Huang. Angew. Chem. Int. Ed. December 19, 2022. 10.1016/10.1002/anie202208936. “New additions to the arsenal of biocatalysts for noncanonical amino acid synthesis” E. Alfonzo, A. Das, and F. H. Arnold. Curr. Opin. Green Sustain. Chem. December 2022. 10.1016/j.cogsc.2022.100701. “Enzymatic Nitrogen Insertion into Unactivated C–H bonds” S. V. Athavale†, S. Gao†, A. Das†, S. C. Mallojjala, E. Alfonzo, Y. Long, J. S. Hirschi, and F. H. Arnold. J. Am. Chem. Soc. October 4, 2022. 10.1021/jacs.2c08285. Perspective by Derek Lowe: Zapping in Amine Groups. Synfacts highlight: Enzymatic Amination and Amidation of Unactivated Csp3–H Sites. “In vivo hypermutation and continuous evolution” R. S. Molina, G. Rix, A. A. Mengiste, B. Álvarez, D. Seo, H. Chen, J. E. Hurtado, Q. Zhang, J. D. García-García, Z. J. Heins, P. J. Almhjell, F. H. Arnold, A. S. Khalil, A. D. Hanson, J. E. Dueber, D. V. Schaffer, F. Chen, S. Kim, L. Á. Fernández, M. D. Shoulders & C. C. Liu. Nat. Rev.…