Interaction Between Nucleoside Diphosphate Kinase And Graphene Oxide And Its Impact On Cardiovascular Diseases
Authors
Singh, Shrishti
Ray, Anushka
Silwal, Sushila
Macwan, Isaac
Patra, Prabir
Issue Date
2017-03-24
Type
Presentation
Language
en_US
Keywords
Cardiovascular disease , Graphene oxide , Nucleoside diphosphate kinase
Alternative Title
Abstract
Here we report possibly for the first time the computational understanding of the interactions between the nanomaterial Graphene Oxide (GO) and the enzyme Nuclear Diphosphate Kinase (NDPK) and its implications. Nanoscale Molecular Dynamics (NAMD) and Visual Molecular Dynamics (VMD) were used to run simulations and analyze the interactions between NDPK and GO. The simulations have run for 100 ns, and it is observed that GO is able to block the active site of the enzyme. Graphene oxide is being used because of its excellent biocompatibility, high water dispersibility, and large surface area. NDPK has numerous roles in the body, such as activating G-proteins and transferring a phosphate from ATP to GDP (resulting in ADP and GTP). It also plays a role in cell proliferation, development, signal transduction, endocytosis, etc[2]. Normally, increased activity of NDPK yields the synthesis of the second messenger cyclic adenosine monophosphate (cAMP) . However, during heart failure, NDPK suppresses cAMP formation due to altered signal transduction pathways via G-proteins. In a healthy heart, nitric oxide (NO) is produced by the body in the endothelium that lines the walls of blood vessels so that the veins and arteries can dilate and blood can flow through the body. However, during heart failure, the endothelium lining is damaged, which inhibits the production of NO. cAMP signal transduction pathways have the potential to produce NO after the endothelium lining is in the process of being damaged . Therefore, when NDPK suppresses cAMP during heart failure, it in turn inhibits the production of nitric oxide— which is crucial for a healthy heart. Using NAMD simulations and analysis using VMD, it is observed that graphene oxide is attracted to the active site of NDPK. Strong interactive forces (van der Waals forces) exist between the primary residue of the active site of NDPK (histidine 118) and graphene oxide. Also, throughout the simulation, the structure of the enzyme is preserved. From the 100 ns worth of simulation, it is observed that the graphene oxide blocks the primary residue of the active site of NDPK and can therefore cease the enzyme’s function, lower the rate of reaction, and potentially affect heart failure.