AI-based IsAb2.0 for antibody design.

Autor: Liang T; Department of Pharmaceutical Sciences, Computational Chemical Genomics Screening Center, Pharmacometrics & System Pharmacology PharmacoAnalytics, School of Pharmacy, University of Pittsburgh, 335 Sutherland Drive, Pittsburgh, PA 15261, United States.; National Center of Excellence for Computational Drug Abuse Research, University of Pittsburgh, 3501 Terrace St, Pittsburgh, PA 15261, United States.; Drug Discovery Institute, University of Pittsburgh, 3501 Terrace St, Pittsburgh, PA 15261, United States.; Department of Computational Biology, School of Medicine, University of Pittsburgh, 3420 Forbes Avenue, Pittsburgh, PA 15261, United States.; Department of Structural Biology, School of Medicine, University of Pittsburgh, 3501 Fifth Ave, Pittsburgh, PA 15261, United States., Sun ZY; Department of Pharmaceutical Sciences, Computational Chemical Genomics Screening Center, Pharmacometrics & System Pharmacology PharmacoAnalytics, School of Pharmacy, University of Pittsburgh, 335 Sutherland Drive, Pittsburgh, PA 15261, United States.; National Center of Excellence for Computational Drug Abuse Research, University of Pittsburgh, 3501 Terrace St, Pittsburgh, PA 15261, United States.; Drug Discovery Institute, University of Pittsburgh, 3501 Terrace St, Pittsburgh, PA 15261, United States.; Department of Computational Biology, School of Medicine, University of Pittsburgh, 3420 Forbes Avenue, Pittsburgh, PA 15261, United States.; Department of Structural Biology, School of Medicine, University of Pittsburgh, 3501 Fifth Ave, Pittsburgh, PA 15261, United States., Hines MG; Division of Infectious Diseases, Department of Medicine, Center for Antibody Therapeutics, School of Medicine, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA, United States., Penrose KJ; Division of Infectious Diseases, Department of Medicine, Center for AIDS Research, School of Medicine, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA, United States., Hao Y; Department of Pharmaceutical Sciences, Computational Chemical Genomics Screening Center, Pharmacometrics & System Pharmacology PharmacoAnalytics, School of Pharmacy, University of Pittsburgh, 335 Sutherland Drive, Pittsburgh, PA 15261, United States.; National Center of Excellence for Computational Drug Abuse Research, University of Pittsburgh, 3501 Terrace St, Pittsburgh, PA 15261, United States.; Drug Discovery Institute, University of Pittsburgh, 3501 Terrace St, Pittsburgh, PA 15261, United States.; Department of Computational Biology, School of Medicine, University of Pittsburgh, 3420 Forbes Avenue, Pittsburgh, PA 15261, United States.; Department of Structural Biology, School of Medicine, University of Pittsburgh, 3501 Fifth Ave, Pittsburgh, PA 15261, United States., Chu X; Division of Infectious Diseases, Department of Medicine, Center for Antibody Therapeutics, School of Medicine, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA, United States., Mellors JW; Division of Infectious Diseases, Department of Medicine, Center for Antibody Therapeutics, School of Medicine, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA, United States.; Division of Infectious Diseases, Department of Medicine, Center for AIDS Research, School of Medicine, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA, United States., Dimitrov DS; Division of Infectious Diseases, Department of Medicine, Center for Antibody Therapeutics, School of Medicine, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA, United States., Xie XQ; Department of Pharmaceutical Sciences, Computational Chemical Genomics Screening Center, Pharmacometrics & System Pharmacology PharmacoAnalytics, School of Pharmacy, University of Pittsburgh, 335 Sutherland Drive, Pittsburgh, PA 15261, United States.; National Center of Excellence for Computational Drug Abuse Research, University of Pittsburgh, 3501 Terrace St, Pittsburgh, PA 15261, United States.; Drug Discovery Institute, University of Pittsburgh, 3501 Terrace St, Pittsburgh, PA 15261, United States.; Department of Computational Biology, School of Medicine, University of Pittsburgh, 3420 Forbes Avenue, Pittsburgh, PA 15261, United States.; Department of Structural Biology, School of Medicine, University of Pittsburgh, 3501 Fifth Ave, Pittsburgh, PA 15261, United States., Li W; Division of Infectious Diseases, Department of Medicine, Center for Antibody Therapeutics, School of Medicine, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA, United States., Feng Z; Department of Pharmaceutical Sciences, Computational Chemical Genomics Screening Center, Pharmacometrics & System Pharmacology PharmacoAnalytics, School of Pharmacy, University of Pittsburgh, 335 Sutherland Drive, Pittsburgh, PA 15261, United States.; National Center of Excellence for Computational Drug Abuse Research, University of Pittsburgh, 3501 Terrace St, Pittsburgh, PA 15261, United States.; Drug Discovery Institute, University of Pittsburgh, 3501 Terrace St, Pittsburgh, PA 15261, United States.; Department of Computational Biology, School of Medicine, University of Pittsburgh, 3420 Forbes Avenue, Pittsburgh, PA 15261, United States.; Department of Structural Biology, School of Medicine, University of Pittsburgh, 3501 Fifth Ave, Pittsburgh, PA 15261, United States.
Jazyk: angličtina
Zdroj: Briefings in bioinformatics [Brief Bioinform] 2024 Jul 25; Vol. 25 (5).
DOI: 10.1093/bib/bbae445
Abstrakt: Therapeutic antibody design has garnered widespread attention, highlighting its interdisciplinary importance. Advancements in technology emphasize the critical role of designing nanobodies and humanized antibodies in antibody engineering. However, current experimental methods are costly and time-consuming. Computational approaches, while progressing, faced limitations due to insufficient structural data and the absence of a standardized protocol. To tackle these challenges, our lab previously developed IsAb1.0, an in silico antibody design protocol. Yet, IsAb1.0 lacked accuracy, had a complex procedure, and required extensive antibody bioinformation. Moreover, it overlooked nanobody and humanized antibody design, hindering therapeutic antibody development. Building upon IsAb1.0, we enhanced our design protocol with artificial intelligence methods to create IsAb2.0. IsAb2.0 utilized AlphaFold-Multimer (2.3/3.0) for accurate modeling and complex construction without templates and employed the precise FlexddG method for in silico antibody optimization. Validated through optimization of a humanized nanobody J3 (HuJ3) targeting HIV-1 gp120, IsAb2.0 predicted five mutations that can improve HuJ3-gp120 binding affinity. These predictions were confirmed by commercial software and validated through binding and neutralization assays. IsAb2.0 streamlined antibody design, offering insights into future techniques to accelerate immunotherapy development.
(© The Author(s) 2024. Published by Oxford University Press.)
Databáze: MEDLINE
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