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A small change, a big impact: How to improve focus through energy?
In biochemical reactions, error correction is a crucial mechanism to ensure reaction accuracy. This mechanism is made possible by the concept of "kinetic correction", a term first coined by John Hopfield and Jacques Ninho in the 1970s. This article will explore in depth the principles of kinetic correction and how it can enhance the specificity of organisms through the introduction of energy, thereby changing our understanding of how life works.
Kinetic correction is a mechanism that allows enzymes to discriminate between correct and incorrect reaction pathways, thereby improving their accuracy beyond predictions that rely solely on free energy differences.
Basic principles of dynamic correction
Kinetic correction can improve the specificity of the correct product that has been selected by introducing an irreversible step that makes it easier for the erroneous reaction intermediate to exit the reaction pathway prematurely. For example, if a production line sometimes produces empty boxes and we cannot upgrade the line, we can increase the ratio of full boxes to empty boxes by placing fans at the end of the line. We can achieve this increase in specificity because empty boxes have a higher chance of being blown away.In biomolecules, kinetic correction can greatly improve the specificity between different reaction pathways, especially during protein synthesis. Since the differences between the sequences of the faulty genes are minimal, it is impossible to achieve such high accuracy by relying solely on energy differences for identification. The specificity paradox in protein synthesis Hopfield pointed out that the error rate in protein synthesis is about 10^(-4). This means that when the ribosome matches the anticodon of the tRNA with the codon of the mRNA, almost all of the pairing is correct. However, this is difficult to achieve in a single-step mechanism. Because if the enzyme mistakenly binds to the wrong tRNA, it will not be able to rely on energy matching alone to recognize it.The key to kinetic correction is to introduce energy to ensure that the steps are irreversible, thereby increasing the specificity of the entry and exit pathways.
The solution to this error is kinetic correction, a mechanism that can improve specificity by introducing an irreversible step in the reaction through energy input.With the introduction of multiple detection, the gradual reduction in error rate makes it theoretically feasible to improve specificity.
The concept of multi-step chain
Hopfield also proposed a simple method to reduce the error rate through a multi-step reaction chain. In this process, each irreversible step consumes energy, and a comparison is performed in each step. Continuous steps enhance the effect of the comparison.The energy required for this so-called multistep chain reaction is to ensure that the entry and exit pathways are largely separate, thereby eliminating the need to rely on a balance-based approach to get rid of the wrong substrates.By cyclically checking through countless irreversible steps, consuming energy at each step, the ratio of correct substrates to incorrect substrates can be substantially increased.
Experimental Examples
Let's look at some specific experimental examples that use the principle of dynamic correction:The amino acid synthetase that charges tRNA improves the pairing accuracy of tRNA and amino acids by introducing high-energy intermediates.
Homologous recombination involves the recruitment of the RecA protein and its search for compatible DNA sequences, a process that also employs kinetic correction.
During the DNA repair process, specific DNA polymerases can detect and rapidly hydrolyze incorrect bases to make corrections.
T cell receptors use kinetic calibration to recognize high and low affinity antigens, and multiple phosphorylation steps are used to enhance recognition accuracy.
Theoretical considerations
These biochemical processes that exploit kinetic corrections to enhance specificity have been observed to exhibit a cosmic-like exponential shape in reaction times. This exponential completion time suggests that kinetic correction is one of the few biochemical processes that exploits structural complexity to reduce the complexity of large-scale processes.However, it also suggests that understanding the relationship between structure and function in complex molecular networks will have a profound impact on our understanding of the core workings of life.As the number of reorganization paths increases, the impact on specificity increases, and the network topology will inevitably have a significant impact on it.
When we consider the inner workings of these biochemical mechanisms, we can't help but wonder what profound effects these small changes could have on the evolution of life.
