New Methods to Improve Protein Structure Modeling

Proteins are considered the central compound necessary for life, as they play a crucial role in governing several life processes by performing the most essential biological and chemical functions in every living cell. Understanding protein structures and functions will lead to a significant advance in life science and biology. Such knowledge is vital for various fields such as drug development and synthetic biofuels production. Most proteins have definite shapes that they fold into, which are the most stable state they can adopt. Due to the fact that the protein structure information provides important insight into its functions, many research efforts have been conducted to determine the protein 3-dimensional structure from its sequence. The experimental methods for protein 3-dimensional structure determination are often time-consuming, costly, and even not feasible for some proteins. Accordingly, recent research efforts focus more and more on computational approaches to predict protein 3-dimensional structures. Template-based modeling is considered one of the most accurate protein structure prediction methods. The success of template-based modeling relies on correctly identifying one or a few experimentally determined protein structures as structural templates that are likely to resemble the structure of the target sequence as well as accurately producing a sequence alignment that maps the residues in the target sequence to those in the template. In this work, we aim at improving the template-based protein structure modeling by enhancing the correctness of identifying the most appropriate templates and precisely aligning the target and template sequences. Firstly, we investigate employing inter-residue contact score to measure the favorability of a target sequence fitting in the folding topology of a certain template. Secondly, we design a multi-objective alignment algorithm extending the famous Needleman-Wunsch algorithm to obtain a complete set of alignments yielding Pareto optimality. Then, we use protein sequence and structural information as objectives and generate the complete Pareto optimal front of alignments between target sequence and template. The alignments obtained enable one to analyze the trade-offs between the potentially conflicting objectives. These approaches lead to accuracy enhancement in template-based protein structure modeling

Parallel Exchange of Randomized SubGraphs for Optimization of Network Alignment: PERSONA

The aim of Network Alignment in Protein-Protein Interaction Networks is discovering functionally similar regions between compared organisms. One major compromise for solving a network alignment problem is the trade-off among multiple similarity objectives while applying an alignment strategy. An alignment may lose its biological relevance while favoring certain objectives upon others due to the actual relevance of unfavored objectives. One possible solution for solving this issue may be blending the stronger aspects of various alignment strategies until achieving mature solutions. This study proposes a parallel approach called PERSONA that allows aligners to share their partial solutions continuously while they progress. All these aligners pursue their particular heuristics as part of a particle swarm that searches for multi-objective solutions of the same alignment problem in a reactive actor environment. The actors use the stronger portion of a solution as a subgraph that they receive from leading or other actors and send their own stronger subgraphs back upon evaluation of those partial solutions. Moreover, the individual heuristics of each actor takes randomized parameter values at each cycle of parallel execution so that the problem search space can thoroughly be investigated. The results achieved with PERSONA are remarkably optimized and balanced for both topological and node similarity objectives

Revealing divergent evolution, identifying circular permutations and detecting active-sites by protein structure comparison

BACKGROUND: Protein structure comparison is one of the most important problems in computational biology and plays a key role in protein structure prediction, fold family classification, motif finding, phylogenetic tree reconstruction and protein docking. RESULTS: We propose a novel method to compare the protein structures in an accurate and efficient manner. Such a method can be used to not only reveal divergent evolution, but also identify circular permutations and further detect active-sites. Specifically, we define the structure alignment as a multi-objective optimization problem, i.e., maximizing the number of aligned atoms and minimizing their root mean square distance. By controlling a single distance-related parameter, theoretically we can obtain a variety of optimal alignments corresponding to different optimal matching patterns, i.e., from a large matching portion to a small matching portion. The number of variables in our algorithm increases with the number of atoms of protein pairs in almost a linear manner. In addition to solid theoretical background, numerical experiments demonstrated significant improvement of our approach over the existing methods in terms of quality and efficiency. In particular, we show that divergent evolution, circular permutations and active-sites (or structural motifs) can be identified by our method. The software SAMO is available upon request from the authors, or from and . CONCLUSION: A novel formulation is proposed to accurately align protein structures in the framework of multi-objective optimization, based on a sequence order-independent strategy. A fast and accurate algorithm based on the bipartite matching algorithm is developed by exploiting the special features. Convergence of computation is shown in experiments and is also theoretically proven

Multiobjective characteristic-based framework for very-large multiple sequence alignment

Rubio-Largo, Á., Vanneschi, L., Castelli, M., & Vega-Rodríguez, M. A. (2018). Multiobjective characteristic-based framework for very-large multiple sequence alignment. Applied Soft Computing Journal, 69, 719-736. [Advanced online publication on 27 June 2017]DOI: 10.1016/j.asoc.2017.06.022In the literature, we can find several heuristics for solving the multiple sequence alignment problem. The vast majority of them makes use of flags in order to modify certain alignment parameters; however, if no flags are used, the aligner will run with the default parameter configuration, which, often, is not the optimal one. In this work, we propose a framework that, depending on the biological characteristics of the input dataset, runs the aligner with the best parameter configuration found for another dataset that has similar biological characteristics, improving the accuracy and conservation of the obtained alignment. To train the framework, we use three well-known multiobjective evolutionary algorithms: NSGA-II, IBEA, and MOEA/D. Then, we perform a comparative study between several aligners proposed in the literature and the characteristic-based version of Kalign, MAFFT, and MUSCLE, when solving widely-used benchmarks (PREFAB v4.0 and SABmark v1.65) and very-large benchmarks with thousands of unaligned sequences (HomFam).authorsversionpublishe

DancingLines: An Analytical Scheme to Depict Cross-Platform Event Popularity

Nowadays, events usually burst and are propagated online through multiple modern media like social networks and search engines. There exists various research discussing the event dissemination trends on individual medium, while few studies focus on event popularity analysis from a cross-platform perspective. Challenges come from the vast diversity of events and media, limited access to aligned datasets across different media and a great deal of noise in the datasets. In this paper, we design DancingLines, an innovative scheme that captures and quantitatively analyzes event popularity between pairwise text media. It contains two models: TF-SW, a semantic-aware popularity quantification model, based on an integrated weight coefficient leveraging Word2Vec and TextRank; and wDTW-CD, a pairwise event popularity time series alignment model matching different event phases adapted from Dynamic Time Warping. We also propose three metrics to interpret event popularity trends between pairwise social platforms. Experimental results on eighteen real-world event datasets from an influential social network and a popular search engine validate the effectiveness and applicability of our scheme. DancingLines is demonstrated to possess broad application potentials for discovering the knowledge of various aspects related to events and different media

On subset seeds for protein alignment

We apply the concept of subset seeds proposed in [1] to similarity search in protein sequences. The main question studied is the design of efficient seed alphabets to construct seeds with optimal sensitivity/selectivity trade-offs. We propose several different design methods and use them to construct several alphabets. We then perform a comparative analysis of seeds built over those alphabets and compare them with the standard BLASTP seeding method [2], [3], as well as with the family of vector seeds proposed in [4]. While the formalism of subset seeds is less expressive (but less costly to implement) than the cumulative principle used in BLASTP and vector seeds, our seeds show a similar or even better performance than BLASTP on Bernoulli models of proteins compatible with the common BLOSUM62 matrix. Finally, we perform a large-scale benchmarking of our seeds against several main databases of protein alignments. Here again, the results show a comparable or better performance of our seeds vs. BLASTP.Comment: IEEE/ACM Transactions on Computational Biology and Bioinformatics (2009