Structure and morphology of magnesium channel by coarse-grained monte carlo and molecular dynamics simulations

Abstract

Coarse-grained (CG) models have become a powerful tool for studying biomolecular complex systems with a wide range of potential applications such as large-scale protein motions, protein folding, self-assembly etc. Simulating such behaviors requires time scales which are not practically possible in all-atomistic simulations. This study presents a strategy for the application of CG simulations to investigate structural and morphological properties of cobalt-resistant magnesium channel (CorA) from Thermotoga maritima. Magnesium (Mg2+) plays a crucial function in a variety of physiological processes. The deficiency of magnesium can increase the risk of several health problems, for instance, diabetes, cardiovascular disease and osteoporosis. The transport of Mg2+ across the membrane is primarily facilitated by a specialized family of membrane proteins, called Mg2+ channels. While the molecular mechanism underlying the divalent cation regulation is still a subject of debate, understanding of structure and morphology of Mg2+ channels at the molecular level would provide insight into the fundamental basis of cellular Mg2+ homeostasis. This work has been divided into four parts. The first part explores thermal responses to structural organization of two different lipoprotein nanodiscs using CG molecular dynamics (MD) simulations. The second and third parts demonstrate the applications of CG Monte Carlo simulations to investigate self-organized globular bundles of CorA and the effect of solute matrix on the protein conformation, respectively. For the last part, CGMD simulations were conducted to investigate conformational responses of CorA upon the release of Mg2+.