Theoretical Investigation on the Selective Transport of K Ion and its Blocking in KcsA K Ion Channel

Abstract

Potassium ion channels are distinguished for their fast and selective transport of K+ newlineion newlineacross the cell membrane. The inevitable physiological role of these channels in cell newlinevolume regulation, hormone secretion, neural communication, and muscle cell newlinecontraction makes them the focal point of many types of research. Malfunctions of newlinepotassium channels lead to lethal health conditions. These are primarily treated by newlineblocking K+ newlineion conduction through the channel using blocking agents. A fascinating newlineclass of potassium channel blockers, the quaternary ammonium ion (QA) based newlinemolecules, are the blocking agent of our focus due to their structural tunability. One newlinecan further control the binding and blocking action of QAs by coupling them with a newlinebio-compatible photochromic molecule or photoswitch. The resulting photoswitchable newlinepotassium ion channel blockers are highly sought-after because of their eminent newlinespatiotemporal control. newlineHowever, the role of the amino acids of the potassium ion channel in the selective newlinetransport of K+ newlineion, the influence of alkyl chain length of QAs on its blocking ability, newlinethe confinement effect of the potassium ion channel on the photoswitchable QA, and newlinethe reason behind the observed high blocking ability of E-isomer of photoswitchable newlineQA over its Z-isomer, have eluded explanations. Hence, using computational newlinecalculations, we have shown the importance of amino acids in the ion channel with newlineregard to the selective transport of K+ newlineion and in blocking the ion transport with the newlinementioned channel blockers.