The effect of pH changes on the unfolding force of titin immunoglobulin domain I27 using steered molecular dynamic simulation

Titin is the longest protein found in striated skeletal and cardiac muscle myofibrils. This protein with a length of about 1µm, has multiple domains consisting of PEVK region (proline, glutamic acid, valine, and lysine residues), and immunoglobulin-like (Ig) and fibronectin domains. In muscles, titin owns unique elastic properties in the I-band region and it is responsible for restoration of muscle to its slack length during the passive contractions. I27 (27th immunoglobulin domain) is one of the important regions of titin which has been studied extensively by researchers. An important feature of this region is the connection with calcium ion which charges the region and causes pH to change. In this paper the unfolding force of I27 domain has been investigated by considering various pHs in three states of neutral, acidic and basic, using steered molecular dynamic simulations. The results showed that unfolding stiffness of I27 domain depends significantly on pH changes. It decreases by increasing or decreasing pH value and getting away from the neutral state. In the neutral state the highest value of force is needed to break the hydrogen bonds and start the unfolding process. According to the results, titin’s performance can be improved by changing pH. This proves useful in cases where titin is stiffer than usual or there is a malfunction in the unfolding process.