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.

Estimating exploitable stock biomass for the Maine green sea urchin (Strongylocentrotus droebachiensis) fishery using a spatial statistics approach

The objective of this study was to investigate the spatial patterns in green sea urchin (Strongylocentrotus droebachiensis) density off the coast of Maine, using data from a fishery-independent survey program, to estimate the exploitable biomass of this species. The dependence of sea urchin variables on the environment, the lack of stationarity, and the presence of discontinuities in the study area made intrinsic geostatistics inappropriate for the study; therefore, we used triangulated irregular networks (TINs) to characterize the large-scale patterns in sea urchin density. The resulting density surfaces were modified to include only areas of the appropriate substrate type and depth zone, and were used to calculate total biomass. Exploitable biomass was estimated by using two different sea urchin density threshold values, which made different assumptions about the fishing industry. We observed considerable spatial variability on both small and large scales, including large-scale patterns in sea urchin density related to depth and fishing pressure. We conclude that the TIN method provides a reasonable spatial approach for generating biomass estimates for a fishery unsuited to geostatistics, but we suggest further studies into uncertainty estimation and the selection of threshold density values.