Six aromatic pairs (four Tyr/Tyr, one Tyr/Phe and one Phe/Phe) are present in the selleck beta-hairpin sequences of the Greek keys. Ultraviolet damage to the aromatic residues in lens crystallins may contribute to the genesis of cataract. Mutant proteins with these aromatic residues substituted with alanines

were constructed and expressed in E. coli. All mutant proteins except F115A and F117A had lower thermal stability than the WT protein. In equilibrium experiments in guanidine hydrochloride (GuHCl), all mutant proteins had lower thermodynamic stability than the WT protein. N-terminal domain (N-td) substitutions shifted the N-td transition to lower GuHCl concentration, but the C-terminal domain (C-td) transition remained unaffected. C-td substitutions led to a more cooperative unfolding/refolding process, with both the N-td and C-td transitions shifted to lower GuHCl concentration. The aromatic pairs conserved for each Greek key motif (Greek key pairs) had larger contributions to both thermal stability and thermodynamic stability than the other pairs. Aromatic-aromatic TPCA-1 interaction was estimated as 1.5-2.0 kcal/mol. In kinetic experiments,

N-td substitutions accelerated the early phase of unfolding, while C-td substitutions accelerated the late phase, suggesting independent domain unfolding. Only substitutions of the second Greek key pair of each crystallin domain slowed refolding. The second Greek keys may provide nucleation sites during the folding of the double-Greek-key crystallin domains.”
“Nicotinic acetylcholine receptors contribute to the mediation of cholinergic role in attention, vigilance, orienting and detection of behavioral significant stimuli. We have recently demonstrated an increase of the intrinsic recurrent excitatory activity of the tectum column caused by the phasic (after-burst) nicotinic potentiation of a frog single axon retinotectal transmission to the tectum layer F. We have shown in the present study that the phasic nicotinic potentiation facilitates eliciting of higher activity level of the tectum column featured by generation of output signals

from the tectum column. Since LY3039478 clinical trial these signals can lead to an escape from danger reactions, a functional significance of nicotinic modulation of the neural network has been demonstrated. The phasic nicotinic potentiation that facilitates eliciting of higher activity level of the tectum column can be considered as a mechanism of vigilance and cue detection at the level of small neural network. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“Development of effective methods to screen binary interactions obtained by rigid-body protein-protein docking is key for structure prediction of complexes and for elucidating physicochemical principles of protein-protein binding. We have derived empirical knowledge-based potential functions for selecting rigid-body docking poses.