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Into the Void: Cavities and Tunnels are Essential for Functional Protein Design

Zhang, J.; Peng, Z.

2024-05-10 biophysics
10.1101/2024.05.06.592825 bioRxiv
Show abstract

The design of functional proteins is crucial as it enables the creation of tailored proteins with specific capabilities, unlocking the potential solutions to various biomedical and industrial challenges. The exact relationship between structure, sequence, and function in protein design is intricate, however, a consensus has been reached that the function of a protein is mostly decided by its structure, which further decides its sequence. While the integration of biology with artificial intelligence has propelled significant advancements in protein design and engineering, structure-based functional protein design, especially de novo design, the quest for satisfactory outcomes remains elusive. In this work, we use backbone geometry to represent the cavities and tunnels of functional proteins and show that they are essential for functional protein design. Correct cavity enables specific biophysical processes or biochemical reactions, while appropriate tunnels facilitate the transport of biomolecules or ions. We also provide a package called CAvity Investigation Navigator (CAIN) to help to do the analysis, which is available at https://github.com/JiahuiZhangNCSU/CAIN.

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