Dự đoán cấu trúc protein với độ chính xác cao bằng AlphaFold

Nature - Tập 596 Số 7873 - Trang 583-589 - 2021
John Jumper1, Richard Evans1, Alexander Pritzel1, Tim Green1, Michael Figurnov1, Olaf Ronneberger1, Kathryn Tunyasuvunakool1, Russell Bates1, Augustin Žídek1, Anna Potapenko1, Alex Bridgland1, Clemens Meyer1, Simon Kohl1, Andrew J. Ballard1, Andrew Cowie1, Bernardino Romera‐Paredes1, Stanislav Nikolov1, Rishub Jain1, Jonas Adler1, Trevor Back1, Stig Petersen1, David Reiman1, Ellen Clancy1, Michal Zielinski1, Martin Steinegger2, Michalina Pacholska1, Tamas Berghammer1, Sebastian Bodenstein1, David Silver1, Oriol Vinyals1, Andrew Senior1, Koray Kavukcuoglu1, Pushmeet Kohli1, Demis Hassabis1
1DeepMind, London, UK
2School of Biological Sciences, Seoul National University, Seoul, South Korea

Tóm tắt

Tóm tắtProtein là yếu tố thiết yếu của sự sống, và việc hiểu cấu trúc của chúng có thể tạo điều kiện thuận lợi cho việc hiểu cơ chế hoạt động của chúng. Thông qua một nỗ lực thử nghiệm khổng lồ1–4, cấu trúc của khoảng 100.000 protein độc nhất đã được xác định5, nhưng điều này chỉ đại diện cho một phần nhỏ trong hàng tỷ chuỗi protein đã biết6,7. Phạm vi bao phủ cấu trúc đang bị thắt nút bởi thời gian từ vài tháng đến vài năm cần thiết để xác định cấu trúc của một protein đơn lẻ. Các phương pháp tính toán chính xác là cần thiết để giải quyết vấn đề này và cho phép tin học cấu trúc lớn. Việc dự đoán cấu trúc ba chiều mà một protein sẽ chấp nhận chỉ dựa trên chuỗi axit amin của nó - thành phần dự đoán cấu trúc của 'vấn đề gấp nếp protein'8 - đã là một vấn đề nghiên cứu mở quan trọng trong hơn 50 năm9. Dù đã có những tiến bộ gần đây10–14, các phương pháp hiện tại vẫn chưa đạt đến độ chính xác nguyên tử, đặc biệt khi không có cấu trúc tương đồng nào được biết đến. Tại đây, chúng tôi cung cấp phương pháp tính toán đầu tiên có khả năng dự đoán cấu trúc protein với độ chính xác nguyên tử ngay cả trong trường hợp không có cấu trúc tương tự nào được biết. Chúng tôi đã xác nhận một phiên bản thiết kế hoàn toàn mới của mô hình dựa trên mạng neuron, AlphaFold, trong cuộc thi Đánh giá Cấu trúc Protein Phê bình lần thứ 14 (CASP14)15, cho thấy độ chính xác có thể cạnh tranh với các cấu trúc thử nghiệm trong phần lớn các trường hợp và vượt trội hơn các phương pháp khác đáng kể. Cơ sở của phiên bản mới nhất của AlphaFold là cách tiếp cận học máy mới kết hợp kiến thức vật lý và sinh học về cấu trúc protein, tận dụng các sắp xếp nhiều chuỗi, vào thiết kế của thuật toán học sâu.

Từ khóa

#dự đoán cấu trúc protein #AlphaFold #học máy #mô hình mạng neuron #sắp xếp nhiều chuỗi #bộ đồ chuẩn hóa #chính xác nguyên tử #tin học cấu trúc #vấn đề gấp nếp protein #CASP14

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