Database Permeating through Time, Space, and Medicine: A sequence, structure, and clinical compilation and comparison of transmembrane amino acids in VGL ion channels

Ion channels of the VGL superfamily are extremely diverse in their physiological roles – critical in all excitable cells. Mutations in these channels can cause clinical deficits and symptomologies. With recent advances in sequencing and structural data in the past 30 years, there is a plethora of bioinformatic information that experimentalists can utilize to draw hypotheses about structure and function. However, there is no cohesive database that has compiled this data and presents it in an easily accessible and avoids the confounds of close evolutionary lineages. Here, we seek to fill this gap in resources by compiling and comparing groups of sequences and structures across many channels of the VGL superfamily. Additionally, we corroborate the well-conserved amino acid positions with previous experimental work as well as put forth some understudied but well-conserved amino acid positions that might be fundamental to the certain generalizable mechanisms present in the VGL superfamily channels. To further lend evidence to understudied positions being critical to certain generalizable mechanisms, we also compiled clinical mutation data at these positions across many channels to show the likely functional relevance of these positions. Finally, we will make all of the alignments and resources we generated publicly available at<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://github.com/Frank-Yeh-95/VGLDatabaseCompilation">https://github.com/Frank-Yeh-95/VGLDatabaseCompilation</ext-link>for ease of hypothesis generation.