Energetics and Structural Characterization of the large-scale Functional Motion of Adenylate Kinase

Adenylate Kinase (AK) is a signal transducing protein that regulates cellular energy homeostasis balancing between different conformations. An alteration of its activity can lead to severe pathologies such as heart failure, cancer and neurodegenerative diseases. A comprehensive elucidation of the large-scale conformational motions that rule the functional mechanism of this enzyme is of great value to guide rationally the development of new medications. Here using a metadynamics-based computational protocol we elucidate the thermodynamics and structural properties underlying the AK functional transitions. The free energy estimation of the conformational motions of the enzyme allows characterizing the sequence of events that regulate its action. We reveal the atomistic details of the most relevant enzyme states, identifying residues such as Arg119 and Lys13, which play a key role during the conformational transitions and represent druggable spots to design enzyme inhibitors. Our study offers tools that open new areas of investigation on large-scale motion in proteins.

Nanoelectromechanical DRAM for ultra-large-scale integration (ULSI)

A Nanoelectromechanical (NEM) device developed for dynamic random access memory (DRAM) is reported. A vertical nanotube structure is employed to form the electromechanical switch and capacitor structure. The mechanical movement of the nanotube defines 'On' and 'OFF' states and the electrical signals which result lead to charge storage in a vertical capacitor structure as in a traditional DRAM. The vertical structure contributes greatly to a decrease in cell dimension. The main concept of the NEM switch and capacitor can be applied to other memory devices as well. © 2005 IEEE.