Sann: solvent accessibility prediction of proteins by nearest neighbor method

We present a method to predict the solvent accessibility of proteins which is based on a nearest neighbor method applied to the sequence profiles. Using the method, continuous real-value prediction as well as two-state and three-state discrete predictions can be obtained. The method utilizes the z-score value of the distance measure in the feature vector space to estimate the relative contribution among the k-nearest neighbors for prediction of the discrete and continuous solvent accessibility. The Solvent accessibility database is constructed from 5717 proteins extracted from PISCES culling server with the cutoff of 25% sequence identities. Using optimal parameters, the prediction accuracies (for discrete predictions) of 78.38% (two-state prediction with the threshold of 25%), 65.1% (three-state prediction with the thresholds of 9 and 36%), and the Pearson correlation coefficient (between the predicted and true RSA's for continuous prediction) of 0.676 are achieved An independent benchmark test was performed with the CASP8 targets where we find that the proposed method outperforms existing methods. The prediction accuracies are 80.89% (for two state prediction with the threshold of 25%), 67.58% (three-state prediction), and the Pearson correlation coefficient of 0.727 (for continuous prediction) with mean absolute error of 0.148. We have also investigated the effect of increasing database sizes on the prediction accuracy, where additional improvement in the accuracy is observed as the database size increases. The SANN web server is available at http://lee.kias.re.kr/~newton/sann/.     

Computational resources and tools for antimicrobial peptides

Antimicrobial peptides (AMPs), as evolutionarily conserved components of innate immune system, protect against pathogens including bacteria, fungi, viruses, and parasites. In general, AMPs are relatively small peptides (<10 kDa) with cationic nature and amphipathic structure and have modes of action different from traditional antibiotics. Up to now, there are more than 19 000 AMPs that have been reported, including those isolated from nature sources or by synthesis. They have been considered to be promising substitutes of conventional antibiotics in the quest to address the increasing occurrence of antibiotic resistance. However, most AMPs have modest direct antimicrobial activity, and their mechanisms of action, as well as their structure–activity relationships, are still poorly understood. Computational strategies are invaluable assets to provide insight into the activity of AMPs and thus exploit their potential as a new generation of antimicrobials. This article reviews the advances of AMP databases and computational tools for the prediction and design of new active AMPs. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.     

Recording Single Neurons' Action Potentials from Freely Moving Pigeons Across Three Stages of Learning

While the subject of learning has attracted immense interest from both behavioral and neural scientists, only relatively few investigators have observed single-neuron activity while animals are acquiring an operantly conditioned response, or when that response is extinguished. But even in these cases, observation periods usually encompass only a single stage of learning, i.e. acquisition or extinction, but not both (exceptions include protocols employing reversal learning; see Bingman et al.¹ for an example). However, acquisition and extinction entail different learning mechanisms and are therefore expected to be accompanied by different types and/or loci of neural plasticity.Accordingly, we developed a behavioral paradigm which institutes three stages of learning in a single behavioral session and which is well suited for the simultaneous recording of single neurons'' action potentials. Animals are trained on a single-interval forced choice task which requires mapping each of two possible choice responses to the presentation of different novel visual stimuli (acquisition). After having reached a predefined performance criterion, one of the two choice responses is no longer reinforced (extinction). Following a certain decrement in performance level, correct responses are reinforced again (reacquisition). By using a new set of stimuli in every session, animals can undergo the acquisition-extinction-reacquisition process repeatedly. Because all three stages of learning occur in a single behavioral session, the paradigm is ideal for the simultaneous observation of the spiking output of multiple single neurons. We use pigeons as model systems, but the task can easily be adapted to any other species capable of conditioned discrimination learning.     

SAXSDom: Modeling multidomain protein structures using small-angle X-ray scattering data

Many proteins are composed of several domains that pack together into a complex tertiary structure. Multidomain proteins can be challenging for protein structure modeling, particularly those for which templates can be found for individual domains but not for the entire sequence. In such cases, homology modeling can generate high quality models of the domains but not for the orientations between domains. Small-angle X-ray scattering (SAXS) reports the structural properties of entire proteins and has the potential for guiding homology modeling of multidomain proteins. In this article, we describe a novel multidomain protein assembly modeling method, SAXSDom that integrates experimental knowledge from SAXS with probabilistic Input-Output Hidden Markov model to assemble the structures of individual domains together. Four SAXS-based scoring functions were developed and tested, and the method was evaluated on multidomain proteins from two public datasets. Incorporation of SAXS information improved the accuracy of domain assembly for 40 out of 46 critical assessment of protein structure prediction multidomain protein targets and 45 out of 73 multidomain protein targets from the ab initio domain assembly dataset. The results demonstrate that SAXS data can provide useful information to improve the accuracy of domain-domain assembly. The source code and tool packages are available at https://github.com/jianlin-cheng/SAXSDom .     

Scoring functions in protein folding and design

We present an analysis of the assumptions behind some of the most commonly used methods for evaluating the goodness of the fit between a sequence and a structure. Our studies on a lattice model show that methods based on statistical considerations are easy to use and can capture some of the features of protein-like sequences and their corresponding native states, but unfortunately are incapable of recognizing, with certainty, the native-like conformation of a sequence among a set of decoys. Meanwhile, an optimization method, entailing the determination of the parameters of an effective free energy of interaction, is much more reliable in recognizing the native state of a sequence. However, the statistical method is shown to perform quite well in tests of protein design.     

Observational visuospatial encoding of the cache locations of others by western scrub-jays (<Emphasis Type="Italic">Aphelocoma californica</Emphasis>)

Western scrub-jays (Aphelocoma californica) hide food and rely on spatial memory to recover their caches at a later date. They also rely on observational spatial memory to steal caches made by other individuals. Successful pilfering may require an understanding of allocentric space because the observer will often be in a different position from the demonstrator when the caching event occurs. We compared cache recovery accuracy of pairs of observers that watched a demonstrator cache food. The pattern of recovery searches showed that observers were more accurate when they had observed the caching event from the same viewing direction as the demonstrator than when they had watched from the opposite direction. Search accuracy was not affected by whether or not the tray-specific local cues provided left–right landmark information (i.e. heterogeneous vs. homogeneous local cues), or whether or not the caching tray location was rotated. Taken together, these results suggest that observers have excellent spatial memory and that they have little difficulty with mental rotation.     

HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design

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Automatic imitation in dogs

After preliminary training to open a sliding door using their head and their paw, dogs were given a discrimination task in which they were rewarded with food for opening the door using the same method (head or paw) as demonstrated by their owner (compatible group), or for opening the door using the alternative method (incompatible group). The incompatible group, which had to counterimitate to receive food reward, required more trials to reach a fixed criterion of discrimination performance (85% correct) than the compatible group. This suggests that, like humans, dogs are subject to ‘automatic imitation’; they cannot inhibit online the tendency to imitate head use and/or paw use. In a subsequent transfer test, where all dogs were required to imitate their owners'' head and paw use for food reward, the incompatible group made a greater proportion of incorrect, counterimitative responses than the compatible group. These results are consistent with the associative sequence learning model, which suggests that the development of imitation depends on sensorimotor experience and phylogenetically general mechanisms of associative learning. More specifically, they suggest that the imitative behaviour of dogs is shaped more by their developmental interactions with humans than by their evolutionary history of domestication.