Therefore, we performed molecular inversion probes-next generation sequencing of 5 transient receptor potential cation channels, 8 potassium channels and 2 calcium-activated chloride channel genes in 222 painful- and 304 painless-DN patients. Neuropathic pain is common in diabetic peripheral neuropathy (DN), probably caused by pathogenic ion channel gene variants. Altogether, this indicates that accelerating CTF is a substantial evolutionary force whose interplay with stability and functionality is encoded in secondary structure asymmetry. This correspondence is greater in prokaryotes, which generally require faster protein production. A phenomenological model predicts that CTF can be accelerated by asymmetry in folding rate, up to double the rate, when folding time is commensurate with translation time analysis of the PDB predicts that structural asymmetry is indeed maximal in this regime. Hence, we propose the "slowest-first" scheme, whereby protein sequences evolved structural asymmetry to accelerate CTF: the slowest of the cooperatively folding segments are positioned near the N terminus so they have more time to fold during translation. Furthermore, this α-β asymmetry correlates with sequence length and contact order, both determinants of folding rate, hinting at possible links to co-translational folding (CTF).
![cdock terminal cdock terminal](https://londongateway.blob.core.windows.net/n2cms/upload/Images/About-us/DPWorld-Port-Images-7074.jpg)
![cdock terminal cdock terminal](https://mohawkglobal.com/wp-content/uploads/2020/04/Long-Beach-Port-1200x630.jpg)
We find remarkable enrichment of α helices at the C terminus and β strands at the N terminus. To explore this question, we analyze 16,200 structures from the Protein Data Bank (PDB). Proteins are translated from the N to the C terminus, raising the basic question of how this innate directionality affects their evolution.