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.

PASREG 2003: International workshop on processing and applications of superconducting (RE)BCO large grain materials

This issue of Superconductor Science and Technology is edited by Murakami, M., Cardwell, D.A., Salama, K., Krabbes, G., Habisreuther, T. and Gawalek, W. It contains 42 selected papers from the PASREG 2003 international workshop, held in Jena, Germany, 30 June - 2 July 2003. The workshop was organised by the Institut fur Physikalische Hochtechnologie, Jena, Germany and was the fourth in the series of workshops first held in Cambridge, UK, in 1997.