Abstract Background Protein structure prediction (PSP) has important applications in different fields, such as drug design, disease prediction, and so on. In protein structure prediction, there are two important issues. The first one is the design of the structure model and the second one is the design of the optimization technology. Because of the complexity of the realistic protein structure, the structure model adopted in this paper is a simplified model, which is called off-lattice AB model. After the structure model is assumed, optimization technology is needed for searching the best conformation of a protein sequence based on the assumed structure model. However, PSP is an NP-hard problem even if the simplest model is assumed. Thus, many algorithms have been developed to solve the global optimization problem. In this paper, a hybrid algorithm, which combines genetic algorithm (GA) and tabu search (TS) algorithm, is developed to complete this task. Results In order to develop an efficient optimization algorithm, several improved strategies are developed for the proposed genetic tabu search algorithm. The combined use of these strategies can improve the efficiency of the algorithm. In these strategies, tabu search introduced into the crossover and mutation operators can improve the local search capability, the adoption of variable population size strategy can maintain the diversity of the population, and the ranking selection strategy can improve the possibility of an individual with low energy value entering into next generation. Experiments are performed with Fibonacci sequences and real protein sequences. Experimental results show that the lowest energy obtained by the proposed GATS algorithm is lower than that obtained by previous methods. Conclusions The hybrid algorithm has the advantages from both genetic algorithm and tabu search algorithm. It makes use of the advantage of multiple search points in genetic algorithm, and can overcome poor hill-climbing capability in the conventional genetic algorithm by using the flexible memory functions of TS. Compared with some previous algorithms, GATS algorithm has better performance in global optimization and can predict 3D protein structure more effectively.

Dearomative cycloaddition reactions represent an ideal means of converting flat arenes into three-dimensional architectures of increasing interest in medicinal chemistry. Quinolines, isoquinolines, and quinazolines, despite containing latent diene and alkene subunits, are scarcely applied in cycloaddition reactions because of the inherent low reactivity of aromatic systems and selectivity challenges. Here, we disclose an energy transfer-mediated, highly regio- and diastereoselective intermolecular [4 + 2] dearomative cycloaddition reaction of these bicyclic azaarenes with a plethora of electronically diverse alkenes. This approach bypasses the general reactivity and selectivity issues, thereby providing various bridged polycycles that previously have been inaccessible or required elaborate synthetic efforts. Computational studies with density functional theory elucidate the mechanism and origins of the observed regio- and diastereoselectivities.

Calbindin-containing γ-aminobutyric acid (GABA)ergic interneurons in the prefrontal cortex (PFC) have been found to play an important role in working memory (WM) and their malfunctions have been linked to psychiatric disorders. A recent genome-wide association and expression-SNP study indicated that the RAB2A gene was associated with the density of prefrontal calbindin-positive neurons, suggesting this gene may have a broader influence on prefrontal structure and function. Using multimodal MRI and behavioral tasks, the current study investigated the effect of RAB2A on prefrontal morphology, resting-state functional connectivity, and WM performance in a large sample of healthy Han Chinese subjects. Results showed that the RAB2A AGCAAA haplotype was associated with improved WM accuracy, increased cortical thickness in the left inferior frontal gyrus, and decreased functional connectivity between the left inferior frontal gyrus and the left dorsolateral PFC. Our findings provide consistent evidence supporting the effect of RAB2A on the structure and function of the PFC and related cognitive functions. These results should provide new insights into the neural mechanisms underlying the GABAergic genes' role in WM as well as its dysfunction.