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.

Remote Camera and Trapping Survey of the Deep-water Shrimps Heterocarpus laevigatus and H. ensifer and the Geryonid Crab Chaceon granulatus in Palau

Time-lapse remote photo-sequences at 73-700 m depth off Palau, Western Caroline Islands, show that the caridean shrimp Heterocarpus laevigatus tends to be a solitary animal, occurring below ~350 m, that gradually accumulates around bait sites over a prolonged period. A smaller speies, H. ensifer, tends to move erratically in swarms, appearing in large numbers in the upper part of its range (<250 m) during the evening crepuscular period and disappearing at dawn. Trapping and photsequence data indicate the depth range of H. ensifer (during daylight) is ~250-550 M, while H. laevigatus ranges from 350 m to at least 800 m, along with the geryonid crab Chaceon granulatus. Combined trapping for Heterocarpus laevigatus and Chaceon granulatus, using a three-chamber box-trap and extended soak times (48-72 hr), may be an appropriate technique for small-scale deep-water fisheries along forereef slopes of Indo-Pacific archipelagoes.

Modelling the entrainment and motion of particles in a gap: Application to abrasive wear

The microscale abrasion or ball-cratering test is being increasingly applied to a wide range of bulk materials and coatings. The response of materials to this test depends critically on the nature of the motion of the abrasive particles in the contact zone: whether they roll and produce multiple indentations in the coating, or slide causing grooving abrasion. Similar phenomena also occur when hard contaminant particles enter a lubricated contact. This paper presents simple quantitative two-dimensional models which describe two aspects of the interaction between a hard abrasive particle and two sliding surfaces. The first model treats the conditions under which a spherical abrasive particle of size d can be entrained into the gap between a rotating sphere of radius R and a plane surface. These conditions are determined by the coefficients of friction between the particle and the sphere, and the particle and the plane, denoted by μs and μp respectively. This model predicts that the values of (μs + μp) and 2μs should both exceed √2d/R for the particles to be entrained into the contact. If either is less than this value, the particle will slide against the sphere and never enter the contact. The second model describes the mechanisms of abrasive wear in a contact when an idealized rhombus-sectioned prismatic particle is located between two parallel plane surfaces separated by a certain distance, which can represent either the thickness of a fluid film or the spacing due to the presence of other particles. It is shown that both the ratio of particle size to the separation of the surfaces and the ratio of the hardnesses of the two surfaces have important influences on the particle motion and hence on the mechanism of the resulting abrasive wear. Results from this model are compared with experimental observations, and the model is shown to lead to realistic predictions. © IMechE 2003.