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An Open Letter from ZuoDong Sun to Professor Roderick MacKinnon

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2026-04-18

Dear Professor Roderick MacKinnon,

Greetings!

Approximately one month ago, I wrote to you for academic advice on issues related to the DNA origami windmill tetramer model, yet received no reply. I am writing again to conduct academic discussions and deliberations with you.

In October 2019, I published the paper The Potassium Channel Origami Windmill Model in the international journal Journal of US-China Medical Science, proposing for the first time the gating mechanism of tetrameric cooperative rotation of potassium ion channels, and putting forward different academic views on the atomic filter model and paddle model founded by you. Recently, in my paper The Gate and Non-Gate of Ion Channels, I also raised theoretical doubts about the stability of gating models based on local bending (such as hinges and levers) under high-frequency and long-term working conditions from the perspectives of engineering reliability and physical dynamics. This has prompted us to consider whether a more holistic and coordinated mechanism (such as cooperative rotation) is needed to explain the remarkable robustness of ion channels.

Your research on the crystal structure of potassium channels published in Science in 1998 revealed the milestone static structure of the atomic filter (selectivity filter), which won you the Nobel Prize in Chemistry in 2003. It is universally recognized and highly respected in the academic community. However, this achievement did not solve the dynamic switching gating mechanism of the channel, which has long been an unresolved key scientific issue in the field.

To fill the gap in gating interpretation, your team proposed the voltage sensor movement mechanism in Nature in 2003, formally establishing the Paddle Model, and further refined it into a hinge, lever, and mechanical coupling system in Science in 2005. The spring reset mechanism often mentioned in academic circles is precisely the mechanical core implied in this series of models, used to explain the reset process after the swing of the S4 "paddle".

In recent years, I have been following the latest progress of your team continuously and noticed that a study published by your research group in May 2025 has experimentally confirmed the existence of four-subunit cooperative movement in potassium ion channels. This important discovery is highly consistent with the core prediction of the origami windmill model I proposed in 2019.

It is worth noting that in the face of the new experimental fact of four-subunit cooperation, you still use the old frameworks formed between 2003 and 2005, such as paddle, hinge, lever, and spring coupling, for interpretation. From the perspective of self-consistency of physical mechanisms, the most concise and non-contradictory physical image of four-subunit cooperative movement is the overall cooperative rotation of the tetramer, rather than the simple superposition of multiple local bends (hinges/levers). The problems of structural fatigue and reset reliability of the local bending mechanism under high-frequency and long-term working conditions still need further theoretical and experimental verification.

From the perspective of scientific context and physical laws: 1998: correct structure, missing gating; 2003–2005: model patching, illogical logic; 2025: experiment confirms cooperation, interpretation still adheres to the old paradigm.

Out of the heart of seeking truth in science, I earnestly consult you on three points again:

1.How can the four-subunit cooperation confirmed by you in 2025 achieve a fully self-consistent physical interpretation under the system of the 1998 atomic filter model and the 2003–2005 paddle/lever/spring/hinge model?

2.As a static structure, is the atomic filter sufficient to fully explain the dynamic gating behavior of potassium ion channels? If not, what is the connection mechanism between it and the subsequent gating models?

3.Do you have specific and clear academic objections to the potassium ion channel "origami windmill" model and the DNA origami windmill tetramer model proposed in 2019?

Science does not ask for seniority, does not avoid authority, and only obeys facts and logic. The real operating mechanism of potassium ion channels awaits your direct or indirect response to the above questions.

I look forward to your guidance at your convenience to jointly promote academic progress.

Sincerely,

 

ZuoDong Sun

April 18, 2026

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