Quick-and-Easy Validation of Protein-Ligand Binding Models Using Fragment-Based Semiempirical Quantum Chemistry.

Electronic structure calculations in enzymes converge very slowly with respect to the size of the model region that is described using quantum mechanics (QM), requiring hundreds of atoms to obtain converged results and exhibiting substantial sensitivity (at least in smaller models) to which amino acids are included in the QM region. As such, there is considerable interest in developing automated procedures to construct a QM model region based on well-defined criteria. However, testing such procedures is burdensome due to the cost of large-scale electronic structure calculations.

Convergent Protocols for Computing Protein-Ligand Interaction Energies Using Fragment-Based Quantum Chemistry.

Fragment-based quantum chemistry methods offer a means to sidestep the steep nonlinear scaling of electronic structure calculations so that large molecular systems can be investigated using high-level methods. Here, we use fragmentation to compute protein-ligand interaction energies in systems with several thousand atoms, using a new software platform for managing fragment-based calculations that implements a screened many-body expansion. Convergence tests using a minimal-basis semiempirical method (HF-3c) indicate that two-body calculations, with single-residue fragments and simple hydrogen caps, are sufficient to reproduce interaction energies obtained using conventional supramolecular electronic structure calculations, to within 1 kcal/mol at about 1% of the computational cost.

Associative learning via eyeblink conditioning differs by age from infancy to adulthood.

Associative learning is a key feature of adaptive behaviour and mental health, enabling individuals to adjust their actions in anticipation of future events. Comprehensive documentation of this essential component of human cognitive development throughout different developmental periods is needed. Here, we investigated age-related changes in associative learning in key developmental stages, including infancy, childhood, adolescence, and adulthood.

Biochemical changes precede affective and cognitive anomalies in aging adult C57BL/6J mice with a prior history of adolescent alcohol binge-drinking.

The early initiation of binge-drinking and biological sex are critical risk factors for the development of affective disturbances and cognitive decline, as well as neurodegenerative diseases including Alzheimer's disease. Further, a history of excessive alcohol consumption alters normal age-related changes in the pattern of protein expression in the brain, which may relate to an acceleration of cognitive decline. Here, we aimed to disentangle the interrelation between a history of binge-drinking during adolescence, biological sex and normal aging on the manifestation of negative affect, cognitive decline and associated biochemical pathology.

Relationship between actigraphy-derived physical activity, sedentary behaviours and sleep parameters in preschool girls and boys: A cross-sectional study.

The aim of the study was to examine associations between moderate-to-vigorous physical activity and sedentary time with sleep quality and quantity among preschool girls and boys using objective methods. Children (5-6 years old) attending kindergarten were recruited (n = 676). Measures included accelerometer-derived 24-hr activity and sleep for seven consecutive days.