Mol ecular Dynamics Simulations Study of Two Single Mutati ons of Coil ۲B of Hu man Lamin A/C

Lamin s are the major constituents of a filamentous network of proteins, un derling the inner nuclea r membran e, termed nuclear lamin a. They are grouped as A- and B-type lamins, o n the basis of their bioc hemical pr operties and behavior, d uring mitosis. [۱] Three types of l amins with significant se quence ide ntity are known in human: lamin A/C, B۱ and B ۲. Lamins A and C, encoded by the LMNA gene, form the core scaffold of the nuclear lamina. Dilated cardiomyopathy (DCM) is a condition whereby the normal muscular function of the myoc ardium is altered by spe cific or multiple aetiolog ies. Most of the DCM- related mutations, fall in the Lamin A/C gene in particular i n the Coil ۲ B domain o f the encoded protein. [۲] In this study we hav e applied m olecular dynamics simulations method to investigate the effect of two s ingle mutations (R۳۳۵ W and E۳۴۷ K) on the structural p roperties of lamin’s Coil ۲B domain. In this respect som e structural parameters, involving root mean square devi ations (RMSD), solvent accessible surface area s (SASA) an d gyration radiuses (Rg ) were computed and co mpared.

کلیدواژه ها:

Lamins ، Mutatio n ، Molecular Dynamics Simulation