Insights into the Fold Organization of TIM Barrel from Interaction Energy Based Structure Networks

There are many well-known examples of proteins with low sequence similarity, adopting the same structural fold. This aspect of sequence-structure relationship has been extensively studied both experimentally and theoretically, however with limited success. Most of the studies consider remote homology or ``sequence conservation'' as the basis for their understanding. Recently ``interaction energy'' based network formalism (Protein Energy Networks (PENs)) was developed to understand the determinants of protein structures. In this paper we have used these PENs to investigate the common non-covalent interactions and their collective features which stabilize the TIM barrel fold. We have also developed a method of aligning PENs in order to understand the spatial conservation of interactions in the fold. We have identified key common interactions responsible for the conservation of the TIM fold, despite high sequence dissimilarity. For instance, the central beta barrel of the TIM fold is stabilized by long-range high energy electrostatic interactions and low-energy contiguous vdW interactions in certain families. The other interfaces like the helix-sheet or the helix-helix seem to be devoid of any high energy conserved interactions. Conserved interactions in the loop regions around the catalytic site of the TIM fold have also been identified, pointing out their significance in both structural and functional evolution. Based on these investigations, we have developed a novel network based phylogenetic analysis for remote homologues, which can perform better than sequence based phylogeny. Such an analysis is more meaningful from both structural and functional evolutionary perspective. We believe that the information obtained through the ``interaction conservation'' viewpoint and the subsequently developed method of structure network alignment, can shed new light in the fields of fold organization and de novo computational protein design.

PLIC: protein-ligand interaction clusters

Most of the biological processes are governed through specific protein-ligand interactions. Discerning different components that contribute toward a favorable protein-ligand interaction could contribute significantly toward better understanding protein function, rationalizing drug design and obtaining design principles for protein engineering. The Protein Data Bank (PDB) currently hosts the structure of similar to 68 000 protein-ligand complexes. Although several databases exist that classify proteins according to sequence and structure, a mere handful of them annotate and classify protein-ligand interactions and provide information on different attributes of molecular recognition. In this study, an exhaustive comparison of all the biologically relevant ligand-binding sites (84 846 sites) has been conducted using PocketMatch: a rapid, parallel, in-house algorithm. PocketMatch quantifies the similarity between binding sites based on structural descriptors and residue attributes. A similarity network was constructed using binding sites whose PocketMatch scores exceeded a high similarity threshold (0.80). The binding site similarity network was clustered into discrete sets of similar sites using the Markov clustering (MCL) algorithm. Furthermore, various computational tools have been used to study different attributes of interactions within the individual clusters. The attributes can be roughly divided into (i) binding site characteristics including pocket shape, nature of residues and interaction profiles with different kinds of atomic probes, (ii) atomic contacts consisting of various types of polar, hydrophobic and aromatic contacts along with binding site water molecules that could play crucial roles in protein-ligand interactions and (iii) binding energetics involved in interactions derived from scoring functions developed for docking. For each ligand-binding site in each protein in the PDB, site similarity information, clusters they belong to and description of site attributes are provided as a relational database-protein-ligand interaction clusters (PLIC).

Accurate prediction of interfacial residues in two-domain proteins using evolutionary information: Implications for three-dimensional modeling

With the preponderance of multidomain proteins in eukaryotic genomes, it is essential to recognize the constituent domains and their functions. Often function involves communications across the domain interfaces, and the knowledge of the interacting sites is essential to our understanding of the structure-function relationship. Using evolutionary information extracted from homologous domains in at least two diverse domain architectures (single and multidomain), we predict the interface residues corresponding to domains from the two-domain proteins. We also use information from the three-dimensional structures of individual domains of two-domain proteins to train naive Bayes classifier model to predict the interfacial residues. Our predictions are highly accurate (approximate to 85%) and specific (approximate to 95%) to the domain-domain interfaces. This method is specific to multidomain proteins which contain domains in at least more than one protein architectural context. Using predicted residues to constrain domain-domain interaction, rigid-body docking was able to provide us with accurate full-length protein structures with correct orientation of domains. We believe that these results can be of considerable interest toward rational protein and interaction design, apart from providing us with valuable information on the nature of interactions. Proteins 2014; 82:1219-1234. (c) 2013 Wiley Periodicals, Inc.

Re-analysis of cryoEM data on HCV IRES bound to 40S subunit of human ribosome integrated with recent structural information suggests new contact regions between ribosomal proteins and HCV RNA

In this study, we combine available high resolution structural information on eukaryotic ribosomes with low resolution cryo-EM data on the Hepatitis C Viral RNA (IRES) human ribosome complex. Aided further by the prediction of RNA-protein interactions and restrained docking studies, we gain insights on their interaction at the residue level. We identified the components involved at the major and minor contact regions, and propose that there are energetically favorable local interactions between 40S ribosomal proteins and IRES domains. Domain II of the IRES interacts with ribosomal proteins S5 and S25 while the pseudoknot and the downstream domain IV region bind to ribosomal proteins S26, S28 and S5. We also provide support using UV cross-linking studies to validate our proposition of interaction between the S5 and IRES domains II and IV. We found that domain IIIe makes contact with the ribosomal protein S3a (S1e). Our model also suggests that the ribosomal protein S27 interacts with domain IIIc while S7 has a weak contact with a single base RNA bulge between junction IIIabc and IIId. The interacting residues are highly conserved among mammalian homologs while IRES RNA bases involved in contact do not show strict conservation. IRES RNA binding sites for S25 and S3a show the best conservation among related viral IRESs. The new contacts identified between ribosomal proteins and RNA are consistent with previous independent studies on RNA-binding properties of ribosomal proteins reported in literature, though information at the residue level is not available in previous studies.

Social insect colony as a biological regulatory system: modelling information flow in dominance networks

Social insects provide an excellent platform to investigate flow of information in regulatory systems since their successful social organization is essentially achieved by effective information transfer through complex connectivity patterns among the colony members. Network representation of such behavioural interactions offers a powerful tool for structural as well as dynamical analysis of the underlying regulatory systems. In this paper, we focus on the dominance interaction networks in the tropical social wasp Ropalidia marginata-a species where behavioural observations indicate that such interactions are principally responsible for the transfer of information between individuals about their colony needs, resulting in a regulation of their own activities. Our research reveals that the dominance networks of R. marginata are structurally similar to a class of naturally evolved information processing networks, a fact confirmed also by the predominance of a specific substructure-the `feed-forward loop'-a key functional component in many other information transfer networks. The dynamical analysis through Boolean modelling confirms that the networks are sufficiently stable under small fluctuations and yet capable of more efficient information transfer compared to their randomized counterparts. Our results suggest the involvement of a common structural design principle in different biological regulatory systems and a possible similarity with respect to the effect of selection on the organization levels of such systems. The findings are also consistent with the hypothesis that dominance behaviour has been shaped by natural selection to co-opt the information transfer process in such social insect species, in addition to its primal function of mediation of reproductive competition in the colony.

Laboratory-frame observables for probing the top-Higgs boson interaction

We investigate methods to explore the CP nature of the t (t) over barh coupling at the LHC, focusing on associated production of the Higgs boson with a t (t) over bar pair. We first discuss the constraints implied by low-energy observables and by the Higgs-rate information from available LHC data, emphasizing that they cannot provide conclusive evidence on the nature of this coupling. We then investigate kinematic observables that could probe the t (t) over barh coupling directly, in particular, quantities that can be constructed out of just laboratory-frame kinematics. We define one such observable by exploiting the fact that t (t) over bar spin correlations do also carry information about the CP nature of the t (t) over barh coupling. Finally, we introduce a CP-odd quantity and a related asymmetry, able to probe CP violation in the t (t) over barh coupling and likewise, constructed out of laboratory-frame momenta only.

Experimental Investigations on Interaction of Two Drops by Thermocapillary-Buoyancy Migration

Experiments were performed, in a terrestrial environment, to study the migration and interaction of two drops with different diameters in matrix liquid under temperature gradient field. Pure soybean oil and silicon oil were used as matrix liquid and the drop liquid, respectively. The information on the motions of two drops was recorded by CCD camera system in the experiments to analyze the trajectories and velocities of the drops. Our experiments showed that, upon two drops approaching each other, the influence of the larger drop on the motion of the smaller one became significant. Meanwhile the smaller drop had a little influence on the larger one all the time. The oscillation of migration velocities of both drops was observed as they were approaching. For a short period the smaller drop even moved backward when it became side by side with the larger one during the migration. Although our experimental results on the behavior of two drops are basically consistent with the theoretical predictions, there are also apparent differences. 2006 Elsevier Ltd. All rights reserved. Keywords: Thermocapillary migration; Drop; Interaction; Oscillation 1. Introduction A bubble or drop will move when placed in another fluid with temperature gradient. This motion happens as a consequence of the variation of interfacial tension with temperature. Such a phenomenon is already known as Marangoni migration problem. With the development of microgravity science, bubble dynamics and droplet dynamics became a hot point problem of research because this investigation is very important for basic research as well as for applications in reduced gravity environment, such as space material science, chemical engineering and so on. Young et al. first investigated the thermocapillary migration of

Skeleton based visual pattern recognition. Applications to tabletop interaction

211 p. :il.

Three essays on economics and information shocks

A person living in an industrialized society has almost no choice but to receive information daily with negative implications for himself or others. His attention will often be drawn to the ups and downs of economic indicators or the alleged misdeeds of leaders and organizations. Reacting to new information is central to economics, but economics typically ignores the affective aspect of the response, for example, of stress or anger. These essays present the results of considering how the affective aspect of the response can influence economic outcomes.

The first chapter presents an experiment in which individuals were presented with information about various non-profit organizations and allowed to take actions that rewarded or punished those organizations. When social interaction was introduced into this environment an asymmetry between rewarding and punishing appeared. The net effects of punishment became greater and more variable, whereas the effects of reward were unchanged. The individuals were more strongly influenced by negative social information and used that information to target unpopular organizations. These behaviors contributed to an increase in inequality among the outcomes of the organizations.

The second and third chapters present empirical studies of reactions to negative information about local economic conditions. Economic factors are among the most prevalent stressors, and stress is known to have numerous negative effects on health. These chapters document localized, transient effects of the announcement of information about large-scale job losses. News of mass layoffs and shut downs of large military bases are found to decrease birth weights and gestational ages among babies born in the affected regions. The effect magnitudes are close to those estimated in similar studies of disasters.

Zooplankton - fish interaction in the littoral zone of Nyanza Gulf, Lake Victoria

The zooplankton community of the littoral zone of Nyanza Gulf, Lake Victoria, was studied between June 1998 and June 1999 to identify and quantify various zooplankton groups, and investigate the interactions that occur between them and the littoral fish through the food chain. Zooplankton samples were collected from five stations using a 83 micro-m mesh size plankton net hauled vertically through the water column. Fish samples were obtained by beach seine, except at Gingra (May 1999), where trawl samples were used. Gut/stomach analysis was carried out on the three major commercial species, Lates niloticus (L.), Oreochromis niloticus (L.) and Rastrineobola argentea (Pellegrin).

The oculomotor system: (1) Vertical-horizontal interaction and signal recognition, (2) Time delays and power spectra

In the first section of this thesis, two-dimensional properties of the human eye movement control system were studied. The vertical - horizontal interaction was investigated by using a two-dimensional target motion consisting of a sinusoid in one of the directions vertical or horizontal, and low-pass filtered Gaussian random motion of variable bandwidth (and hence information content) in the orthogonal direction. It was found that the random motion reduced the efficiency of the sinusoidal tracking. However, the sinusoidal tracking was only slightly dependent on the bandwidth of the random motion. Thus the system should be thought of as consisting of two independent channels with a small amount of mutual cross-talk.

These target motions were then rotated to discover whether or not the system is capable of recognizing the two-component nature of the target motion. That is, the sinusoid was presented along an oblique line (neither vertical nor horizontal) with the random motion orthogonal to it. The system did not simply track the vertical and horizontal components of motion, but rotated its frame of reference so that its two tracking channels coincided with the directions of the two target motion components. This recognition occurred even when the two orthogonal motions were both random, but with different bandwidths.

In the second section, time delays, prediction and power spectra were examined. Time delays were calculated in response to various periodic signals, various bandwidths of narrow-band Gaussian random motions and sinusoids. It was demonstrated that prediction occurred only when the target motion was periodic, and only if the harmonic content was such that the signal was sufficiently narrow-band. It appears as if general periodic motions are split into predictive and non-predictive components.

For unpredictable motions, the relationship between the time delay and the average speed of the retinal image was linear. Based on this I proposed a model explaining the time delays for both random and periodic motions. My experiments did not prove that the system is sampled data, or that it is continuous. However, the model can be interpreted as representative of a sample data system whose sample interval is a function of the target motion.

It was shown that increasing the bandwidth of the low-pass filtered Gaussian random motion resulted in an increase of the eye movement bandwidth. Some properties of the eyeball-muscle dynamics and the extraocular muscle "active state tension" were derived.