After prolonged stress or infection, even when the original cause has been removed, feelings of anxiety, tension, and inner restlessness can continue to linger.
In this report, we reframe this not only as a matter of “psychological state,” but as a molecular state in which the endoplasmic‑reticulum stress response (UPR) fails to switch off.
Our focus is on the protein IRE1α, which sits at the core of the stress‑response network.
In the short term, this molecule protects the cell, but when activation is prolonged, it may continuously stimulate pathways related to inflammation and anxiety.
In this study, we combined:
 
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Verification of simultaneous binding of multiple molecules by multi‑ligand MD
Quantitative evaluation of αC–DFG geometry and salt‑bridge stability
 
to explore the structural conditions under which IRE1α overactivity can be quietly loosened.
By comparing roughly 200 different simulation conditions, we found that, for certain combinations,
the structures that support the stress response became consistently destabilized.
This report is not intended as a tool for medical intervention or treatment.
However, it provides one kind of map for understanding, at the molecular level, “why the sense of safety does not come back.”
It is an in silico research report for people suffering from Long COVID, chronic stress, or persistent anxiety, and for those who wish to understand the background of these states in a theoretical way.
(Discount available until February 13, 2026.)
 
Physiological Mechanisms Evaluated
Endoplasmic‑reticulum stress response (UPR)
Structural modulation of IRE1α kinase / RNase activity
αC–DFG orientation and salt‑bridge stability
 
Intended Readers
People whose anxiety or tension has persisted after Long COVID
People who feel they cannot easily escape from a state of chronic stress
People who want to understand the background at a physiological / molecular level
People in medical, research, or technical professions who seek a theoretical perspective
 
⚠ People Who Should Exercise Caution
This report is not intended to provide medical acts, diagnosis, or treatment.
It does not recommend the intake of any supplements or ingredients.
If you have chronic illnesses, are currently undergoing treatment, or are pregnant or breastfeeding,
please consult a physician or pharmacist before considering any new intervention.
This report is an in silico (computer‑simulation) study.
 
Disclaimer
※ This report is intended to provide knowledge about molecular mechanisms and physicochemical insights.
It is not intended as a recommendation of any specific health food, supplement, pharmaceutical product, etc., nor as medical advice.
※ When making actual decisions about introducing or using any product or intervention,
please always consult qualified physicians or other healthcare professionals.