Conformational penalties: The other half of molecular recognition
At the most fundamental level, living organisms are the product of biomolecules interacting with one another through a process commonly referred to as molecular recognition. To understand how biomolecule interact with one another, we need a framework that describes those properties of the biomolecules that determine their binding affinities and specificities. Our current understanding dates back six decades ago when Linus Pauling proposed that specificity is achieved through the structural complementarity of the binding partners. This concept has been reinforced over the decades thanks to advances in the determination of high-resolution structures of biomolecules by X-ray crystallography and cryoEM. Static structures only carry information regarding one half of the molecular recognition equation, which I will refer to as income. This half describes the favorable contacts formed upon complex formation. The second half, which has received much less attention, I will refer to as income tax. It represents the energetic cost associated with changing the structure of a biomolecule from one form to another when binding a partner molecule. Unlike income, the income tax half of the molecular recognition equation can only be determined experimentally through an ensemble description of biomolecules as a probability distribution of many different conformations. I will argue that income tax, and mechanisms for tax evasion, are ubiquitous in biology and disease, drawing on DNA replication as a primary example.
https://www.nature.com/articles/s41586-020-2843-2
https://sites.duke.edu/alhashimilab/research/
free energy tax
distribution of the sub-states really affect taxation of free energy. Mentioned to use MD to run and get distribution of molecules, keep the caveat that it might not reflect experimental results.
TF factors and motifs:: specificity and affinity are generally correlated, but can be altered.
free engery and probability landscape is connected by logrithm
Tax impairs DNA replication forks and increases DNA breaks in specific oncogenic genome regions
Hassiba Chaib-Mezrag, Delphine Lemaçon, Hélène Fontaine, Marcia Bellon, Xue Tao Bai, Marjorie Drac, Arnaud Coquelle, and Christophe Nicot
. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4168069/"Free energy minimisation is equivalent to maximising the mutual information between sensory states and internal states that parameterise the variational density (for a fixed entropy variational density).[11][better source needed] This relates free energy minimization to the principle of minimum redundancy[25] and related treatments using information theory to describe optimal behaviour."
This is related to our cross-entropy work on aging analysis
Kullback-Leibler divergence, or relative entropy
https://en.wikipedia.org/wiki/Relative_entropy
active inference by Karl Friston
Re Friston: a good intro talk: https://www.santafe.edu/events/me-and-my-markov-blanket
what’s the authors name of the self replicating machine?
von Neumann
The book that was cited is called "The theory of self-reproducing automata"
Here’s Art Burk’s review of von Neumann: http://walterfontana.zone/wp-content/uploads/2020/12/Burks-1969.pdf
https://www.sciencedirect.com/science/article/pii/S2405471218300577
This paper does exactly that on the Lac repressor
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