Structure-based substrate screening for an enzyme

<p>Abstract</p> <p>Background</p> <p>Nowadays, more and more novel enzymes can be easily found in the whole enzyme pool with the rapid development of genetic operation. However, experimental work for substrate screening of a new enzyme is laborious, time consuming and costly. On the other hand, many computational methods have been widely used in lead screening of drug design. Seeing that the ligand-target protein system in drug design and the substrate-enzyme system in enzyme applications share the similar molecular recognition mechanism, we aim to fulfill the goal of substrate screening by in silico means in the present study.</p> <p>Results</p> <p>A computer-aided substrate screening (CASS) system which was based on the enzyme structure was designed and employed successfully to help screen substrates of <it>Candida antarctica </it>lipase B (CALB). In this system, restricted molecular docking which was derived from the mechanism of the enzyme was applied to predict the energetically favorable poses of substrate-enzyme complexes. Thereafter, substrate conformation, distance between the oxygen atom of the alcohol part of the ester (in some compounds, this oxygen atom was replaced by nitrogen atom of the amine part of acid amine or sulfur atom of the thioester) and the hydrogen atom of imidazole of His224, distance between the carbon atom of the carbonyl group of the compound and the oxygen atom of hydroxyl group of Ser105 were used sequentially as the criteria to screen the binding poses. 223 out of 233 compounds were identified correctly for the enzyme by this screening system. Such high accuracy guaranteed the feasibility and reliability of the CASS system.</p> <p>Conclusion</p> <p>The idea of computer-aided substrate screening is a creative combination of computational skills and enzymology. Although the case studied in this paper is tentative, high accuracy of the CASS system sheds light on the field of computer-aided substrate screening.</p

Analysis of the Arabidopsis thaliana mutant constitutive expression of vegetative storage protein, cev2

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Circumscribed Interest Modulates Attention to Eyes in Boys With and Without Autism Spectrum Disorder

Children with autism spectrum disorder (ASD) exhibit abnormal visual attention, such as diminished attention to eyes and enhanced attention to high-autism-interest objects. We tested whether high-autism-interest objects would modulate the attention to eyes in boys with ASD and typically developing (TD) boys. Twenty-two ASD and 22 TD children were presented simultaneously with human eyes and high/low-autism-interest objects (HAI/LAI) while their eye movements were recorded. We found that visual preference for eyes was influenced by competing objects in children with and without ASD. Specifically, both children with and without ASD showed reduced overall and first looking preference when eyes were paired with HAI objects relative to LAI objects. Children with ASD also showed reduced sustained viewing preference to the eyes after first looking at the eyes and late looking preference to the eyes after first looking at the objects in the HAI condition than the LAI condition, but these effects were absent in the TD group. Our study not only helps us understand some factors that impact attention to eyes, but also has implications for interventions aiming at improving eye contact in children with ASD.</p

Heterogeneity of Visual Preferences for Biological and Repetitive Movements in Children With Autism Spectrum Disorder

Previous studies have repeatedly reported atypical visual preferences to repetitive movements and deficient perception of biological movements in individuals with autism spectrum disorder (ASD). However, limited research has investigated the heterogeneity of the visual preferences in individuals with ASD. In the current study, we explored the visual preferences to different movement types (repetitive, biological, and random) in children with ASD using a paired preferential looking paradigm. Thirty-nine children with ASD and 37 typically developing (TD) children participated in our study, with their eye movements recorded as the index of visual preferences. We examined the differences of visual preferences between the ASD and TD group, and the heterogeneity of visual preferences within the ASD group. We found group differences between children with ASD and TD children: Overall, the ASD group preferred repetitive movements while the TD group preferred biological movements. We also detected heterogeneity of visual preferences within the ASD group: Although the majority of children with ASD preferred repetitive movements as previous studies reported, 9 out of 39 children with ASD preferred biological movements similarly as their TD peers. Moreover, the visual preference patterns were correlated with autistic symptoms, especially the socio-communicative impairments. Our study provided evidence of heterogeneity of visual attention and main visual preference to repetitive movements in children with ASD. The findings add to the body of literature of the heterogeneous behavioral symptoms and the atypical visual preferences in individuals with ASD. Lay Summary The current study examined visual preferences to biological, repetitive, and random movements in children with Autism Spectrum Disorder (ASD). We showed a pair of two videos representing two types of movements (random, repetitive, or biological movements) to children with ASD and typically developing children. We found the main visual preferences for repetitive movements and heterogeneity of visual attention within the ASD group. Our findings provide theoretical and methodological implications for future study of the heterogeneity in the ASD population.</p

Out of mind, out of sight? Investigating abnormal face scanning in autism spectrum disorder using gaze-contingent paradigm

Diminished social motivation is hypothesized to explain abnormal face scanning pattern in individuals with autism spectrum disorder (ASD), especially reduced eye-looking time in ASDs than typically developing (TD) people. Here, we tested an alternative explanation that children with ASD may use a compensatory strategy to avoid direct eye contact by processing the eyes through peripheral vision. We compared the face scanning patterns of children with and without ASD in two conditions: in the clear condition, the face was completely visible; in the blur condition, by using the gaze-contingent paradigm, the whole face was blurred except for a small region being fixated at, thus children could not rely on the peripheral information to process the eyes. We found that children with ASD fixated less on the eyes than TD children in both conditions. Temporal-course analyses further revealed the possible motivation-based guidance of attention to process the eyes in the TD group but not in the ASD group. Additionally, we found that children with ASD scanned faces more randomly and less strategically than TD children. These results have ruled out the alternative hypothesis that the abnormal face scanning pattern in ASDs was due to their compensatory strategy to process eyes through peripheral vision, furthering our understanding of the mechanisms underlying their abnormal face scanning