A network representation of protein structures: Implications for protein stability

This study views each protein structure as a network of noncovalent connections between amino acid side chains. Each amino acid in a protein structure is a node, and the strength of the noncovalent interactions between two amino acids is evaluated for edge determination. The protein structure graphs (PSGs) for 232 proteins have been constructed as a function of the cutoff of the amino acid interaction strength at a few carefully chosen values. Analysis of such PSGs constructed on the basis of edge weights has shown the following: 1), The PSGs exhibit a complex topological network behavior, which is dependent on the interaction cutoff chosen for PSG construction. 2), A transition is observed at a critical interaction cutoff, in all the proteins, as monitored by the size of the largest cluster (giant component) in the graph. Amazingly, this transition occurs within a narrow range of interaction cutoff for all the proteins, irrespective of the size or the fold topology. And 3), the amino acid preferences to be highly connected (hub frequency) have been evaluated as a function of the interaction cutoff. We observe that the aromatic residues along with arginine, histidine, and methionine act as strong hubs at high interaction cutoffs, whereas the hydrophobic leucine and isoleucine residues get added to these hubs at low interaction cutoffs, forming weak hubs. The hubs identified are found to play a role in bringing together different secondary structural elements in the tertiary structure of the proteins. They are also found to contribute to the additional stability of the thermophilic proteins when compared to their mesophilic counterparts and hence could be crucial for the folding and stability of the unique three-dimensional structure of proteins. Based on these results, we also predict a few residues in the thermophilic and mesophilic proteins that can be mutated to alter their thermal stability.

Optimizing Functional Network Representation of Multivariate Time Series

By combining complex network theory and data mining techniques, we provide objective criteria for optimization of the functional network representation of generic multivariate time series. In particular, we propose a method for the principled selection of the threshold value for functional network reconstruction from raw data, and for proper identification of the network's indicators that unveil the most discriminative information on the system for classification purposes. We illustrate our method by analysing networks of functional brain activity of healthy subjects, and patients suffering from Mild Cognitive Impairment, an intermediate stage between the expected cognitive decline of normal aging and the more pronounced decline of dementia. We discuss extensions of the scope of the proposed methodology to network engineering purposes, and to other data mining tasks.

How activation, entanglement, and searching a semantic network contribute to event memory

Free association norms indicate that words are organized into semantic/associative neighborhoods within a larger network of words and links that bind the net together. We present evidence indicating that memory for a recent word event can depend on implicitly and simultaneously activating related words in its neighborhood. Processing a word during encoding primes its network representation as a function of the density of the links in its neighborhood. Such priming increases recall and recognition and can have long lasting effects when the word is processed in working memory. Evidence for this phenomenon is reviewed in extralist cuing, primed free association, intralist cuing, and single-item recognition tasks. The findings also show that when a related word is presented to cue the recall of a studied word, the cue activates it in an array of related words that distract and reduce the probability of its selection. The activation of the semantic network produces priming benefits during encoding and search costs during retrieval. In extralist cuing recall is a negative function of cue-to-distracter strength and a positive function of neighborhood density, cue-to-target strength, and target-to cue strength. We show how four measures derived from the network can be combined and used to predict memory performance. These measures play different roles in different tasks indicating that the contribution of the semantic network varies with the context provided by the task. We evaluate spreading activation and quantum-like entanglement explanations for the priming effect produced by neighborhood density.

Network approach for capturing ligand-induced subtle global changes in protein structures

Ligand-induced conformational changes in proteins are of immense functional relevance. It is a major challenge to elucidate the network of amino acids that are responsible for the percolation of ligand-induced conformational changes to distal regions in the protein from a global perspective. Functionally important subtle conformational changes (at the level of side-chain noncovalent interactions) upon ligand binding or as a result of environmental variations are also elusive in conventional studies such as those using root-mean-square deviations (r.m.s.d.s). In this article, the network representation of protein structures and their analyses provides an efficient tool to capture these variations (both drastic and subtle) in atomistic detail in a global milieu. A generalized graph theoretical metric, using network parameters such as cliques and/or communities, is used to determine similarities or differences between structures in a rigorous manner. The ligand-induced global rewiring in the protein structures is also quantified in terms of network parameters. Thus, a judicious use of graph theory in the context of protein structures can provide meaningful insights into global structural reorganizations upon perturbation and can also be helpful for rigorous structural comparison. Data sets for the present study include high-resolution crystal structures of serine proteases from the S1A family and are probed to quantify the ligand-induced subtle structural variations.

An automated approach to network features of protein structure ensembles

Network theory applied to protein structures provides insights into numerous problems of biological relevance. The explosion in structural data available from PDB and simulations establishes a need to introduce a standalone-efficient program that assembles network concepts/parameters under one hood in an automated manner. Herein, we discuss the development/application of an exhaustive, user-friendly, standalone program package named PSN-Ensemble, which can handle structural ensembles generated through molecular dynamics (MD) simulation/NMR studies or from multiple X-ray structures. The novelty in network construction lies in the explicit consideration of side-chain interactions among amino acids. The program evaluates network parameters dealing with topological organization and long-range allosteric communication. The introduction of a flexible weighing scheme in terms of residue pairwise cross-correlation/interaction energy in PSN-Ensemble brings in dynamical/chemical knowledge into the network representation. Also, the results are mapped on a graphical display of the structure, allowing an easy access of network analysis to a general biological community. The potential of PSN-Ensemble toward examining structural ensemble is exemplified using MD trajectories of an ubiquitin-conjugating enzyme (UbcH5b). Furthermore, insights derived from network parameters evaluated using PSN-Ensemble for single-static structures of active/inactive states of 2-adrenergic receptor and the ternary tRNA complexes of tyrosyl tRNA synthetases (from organisms across kingdoms) are discussed. PSN-Ensemble is freely available from http://vishgraph.mbu.iisc.ernet.in/PSN-Ensemble/psn_index.html.

Genetic algorithms for local controller network construction

Local Controller Networks (LCNs) provide nonlinear control by interpolating between a set of locally valid, subcontrollers covering the operating range of the plant. Constructing such networks typically requires knowledge of valid local models. This paper describes a new genetic learning approach to the construction of LCNs directly from the dynamic equations of the plant, or from modelling data. The advantage is that a priori knowledge about valid local models is not needed. In addition to allowing simultaneous optimisation of both the controller and validation function parameters, the approach aids transparency by ensuring that each local controller acts independently of the rest at its operating point. It thus is valuable for simultaneous design of the LCNs and identification of the operating regimes of an unknown plant. Application results from a highly nonlinear pH neutralisation process and its associated neural network representation are utilised to illustrate these issues.

An Efficient Codification to Solve Distribution Network Reconfiguration for Loss Reduction Problem

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Distribution network reconfiguration using an efficient evolutionary algorithm

Network reconfiguration is an important tool to optimize the operating conditions of a distribution system. This is accomplished modifying the network structure of distribution feeders by changing the open/close status of sectionalizing switches. This not only reduces the power losses, but also relieves the overloading of the network components. Network reconfiguration belongs to a complex family of problems because of their combinatorial nature and multiple constraints. This paper proposes a solution to this problem, using a specialized evolutionary algorithm, with a novel codification, and a brand new way of implement the genetic operators considering the problem characteristics. The algorithm is presented and tested in a real distribution system, showing excellent results and computational efficiency. © 2007 IEEE.

Prominent Effect of Soil Network Heterogeneity on Microbial Invasion

Using a network representation for real soil samples and mathematical models for microbial spread, we show that the structural heterogeneity of the soil habitat may have a very significant influence on the size of microbial invasions of the soil pore space. In particular, neglecting the soil structural heterogeneity may lead to a substantial underestimation of microbial invasion. Such effects are explained in terms of a crucial interplay between heterogeneity in microbial spread and heterogeneity in the topology of soil networks. The main influence of network topology on invasion is linked to the existence of long channels in soil networks that may act as bridges for transmission of microorganisms between distant parts of soil.

Unveiling Protein Functions through the Dynamics of the Interaction Network

Protein interaction networks have become a tool to study biological processes, either for predicting molecular functions or for designing proper new drugs to regulate the main biological interactions. Furthermore, such networks are known to be organized in sub-networks of proteins contributing to the same cellular function. However, the protein function prediction is not accurate and each protein has traditionally been assigned to only one function by the network formalism. By considering the network of the physical interactions between proteins of the yeast together with a manual and single functional classification scheme, we introduce a method able to reveal important information on protein function, at both micro- and macro-scale. In particular, the inspection of the properties of oscillatory dynamics on top of the protein interaction network leads to the identification of misclassification problems in protein function assignments, as well as to unveil correct identification of protein functions. We also demonstrate that our approach can give a network representation of the meta-organization of biological processes by unraveling the interactions between different functional classes

Applying network analysis to the conservation of habitat trees in urban environments: a case study from Brisbane, Australia

In Australia more than 300 vertebrates, including 43 insectivorous bat species, depend on hollows in habitat trees for shelter, with many species using a network of multiple trees as roosts, We used roost-switching data on white-striped freetail bats (Tadarida australis; Microchiroptera: Molossidae) to construct a network representation of day roosts in suburban Brisbane, Australia. Bats were caught from a communal roost tree with a roosting group of several hundred individuals and released with transmitters. Each roost used by the bats represented a node in the network, and the movements of bats between roosts formed the links between nodes. Despite differences in gender and reproductive stages, the bats exhibited the same behavior throughout three radiotelemetry periods and over 500 bat days of radio tracking: each roosted in separate roosts, switched roosts very infrequently, and associated with other bats only at the communal roost This network resembled a scale-free network in which the distribution of the number of links from each roost followed a power law. Despite being spread over a large geographic area (> 200 km(2)), each roost was connected to others by less than three links. One roost (the hub or communal roost) defined the architecture of the network because it had the most links. That the network showed scale-free properties has profound implications for the management of the habitat trees of this roosting group. Scale-free networks provide high tolerance against stochastic events such as random roost removals but are susceptible to the selective removal of hub nodes. Network analysis is a useful tool for understanding the structural organization of habitat tree usage and allows the informed judgment of the relative importance of individual trees and hence the derivation of appropriate management decisions, Conservation planners and managers should emphasize the differential importance of habitat trees and think of them as being analogous to vital service centers in human societies.

Modelling urban public transit users' route choice behaviour: review and outlook

This paper reviews the main development of approaches to modelling urban public transit users’ route choice behaviour from 1960s to the present. The approaches reviewed include the early heuristic studies on finding the least cost transit route and all-or-nothing transit assignment, the bus common line problem and corresponding network representation methods, the disaggregate discrete choice models which are based on random utility maximization assumptions, the deterministic use equilibrium and stochastic user equilibrium transit assignment models, and the recent dynamic transit assignment models using either frequency or schedule based network formulation. In addition to reviewing past outcomes, this paper also gives an outlook into the possible future directions of modelling transit users’ route choice behaviour. Based on the comparison with the development of models for motorists’ route choice and traffic assignment problems in an urban road area, this paper points out that it is rewarding for transit route choice research to draw inspiration from the intellectual outcomes out of the road area. Particularly, in light of the recent advancement of modelling motorists’ complex road route choice behaviour, this paper advocates that the modelling practice of transit users’ route choice should further explore the complexities of the problem.

Construction of Equivalent Circuit of a Single and Isolated Transformer Winding From FRA Data Using the ABC Algorithm

This paper reports the results of employing an artificial bee colony search algorithm for synthesizing a mutually coupled lumped-parameter ladder-network representation of a transformer winding, starting from its measured magnitude frequency response. The existing bee colony algorithm is suitably adopted by appropriately defining constraints, inequalities, and bounds to restrict the search space and thereby ensure synthesis of a nearly unique ladder network corresponding to each frequency response. Ensuring near-uniqueness while constructing the reference circuit (i.e., representation of healthy winding) is the objective. Furthermore, the synthesized circuits must exhibit physical realizability. The proposed method is easy to implement, time efficient, and problems associated with the supply of initial guess in existing methods are circumvented. Experimental results are reported on two types of actual, single, and isolated transformer windings (continuous disc and interleaved disc).

Construction of Equivalent Circuit of a Single and Isolated Transformer Winding From FRA Data Using the ABC Algorithm

This paper reports the results of employing an artificial bee colony search algorithm for synthesizing a mutually coupled lumped-parameter ladder-network representation of a transformer winding, starting from its measured magnitude frequency response. The existing bee colony algorithm is suitably adopted by appropriately defining constraints, inequalities, and bounds to restrict the search space and thereby ensure synthesis of a nearly unique ladder network corresponding to each frequency response. Ensuring near-uniqueness while constructing the reference circuit (i.e., representation of healthy winding) is the objective. Furthermore, the synthesized circuits must exhibit physical realizability. The proposed method is easy to implement, time efficient, and problems associated with the supply of initial guess in existing methods are circumvented. Experimental results are reported on two types of actual, single, and isolated transformer windings (continuous disc and interleaved disc).