The effect of calcium binding on the unfolding force of mutated and healthy titin I10 domain: A steered molecular dynamics simulation study

Abstract

Titin plays an important role in eccentric contraction by creating elastic property in the sarcomere. It can restore muscle to its rest length by stretching and increasing its length. Titin’s structure is made of 244 domains. Due to its position, the I10 domain can be subjected to a mutation which leads to Arrhythmogenic cardiomyopathy. Furthermore, the calcium ion has an important role in muscle contractions by binding to some domains like I10 in titin and accordingly creating changes in the unfolding force of these domains. The purpose of this study was to investigate the effect of calcium binding on the unfolding force of the I10 domain for the normal and mutated states. For this reason, the steered molecular dynamics simulation was performed in different states with various pulling rates. According to the results, calcium binding leads to a rising in the unfolding force of the I10 domain. In addition, mutation decreases the unfolding force of the domain, but the presence of calcium compensates for this effect by raising the unfolding force. Results also indicate that by increasing the pulling rates, the unfolding force would increase considerably.