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NCBI: db=pubmed; Term=(Vakser, Ilya[Author]) OR ((Miao, Yinglong[Author]) AND Kansas) OR (Deeds, Eric[Author]) OR (Ray, Christian[Author]) OR (Slusky, Joanna[Author]) OR (Ray JC[Author] AND Kansas)
Updated: 48 min 39 sec ago

Modeling CAPRI targets 110-120 by template-based and free docking using contact potential and combined scoring function.

Sat, 01/19/2019 - 05:07
Related Articles

Modeling CAPRI targets 110-120 by template-based and free docking using contact potential and combined scoring function.

Proteins. 2018 03;86 Suppl 1:302-310

Authors: Kundrotas PJ, Anishchenko I, Badal VD, Das M, Dauzhenka T, Vakser IA

Abstract
The paper presents analysis of our template-based and free docking predictions in the joint CASP12/CAPRI37 round. A new scoring function for template-based docking was developed, benchmarked on the Dockground resource, and applied to the targets. The results showed that the function successfully discriminates the incorrect docking predictions. In correctly predicted targets, the scoring function was complemented by other considerations, such as consistency of the oligomeric states among templates, similarity of the biological functions, biological interface relevance, etc. The scoring function still does not distinguish well biological from crystal packing interfaces, and needs further development for the docking of bundles of α-helices. In the case of the trimeric targets, sequence-based methods did not find common templates, despite similarity of the structures, suggesting complementary use of structure- and sequence-based alignments in comparative docking. The results showed that if a good docking template is found, an accurate model of the interface can be built even from largely inaccurate models of individual subunits. Free docking however is very sensitive to the quality of the individual models. However, our newly developed contact potential detected approximate locations of the binding sites.

PMID: 28905425 [PubMed - indexed for MEDLINE]

Lineage space and the propensity of bacterial cells to undergo growth transitions.

Sat, 12/29/2018 - 19:06
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Lineage space and the propensity of bacterial cells to undergo growth transitions.

PLoS Comput Biol. 2018 08;14(8):e1006380

Authors: Bandyopadhyay A, Wang H, Ray JCJ

Abstract
The molecular makeup of the offspring of a dividing cell gradually becomes phenotypically decorrelated from the parent cell by noise and regulatory mechanisms that amplify phenotypic heterogeneity. Such regulatory mechanisms form networks that contain thresholds between phenotypes. Populations of cells can be poised near the threshold so that a subset of the population probabilistically undergoes the phenotypic transition. We sought to characterize the diversity of bacterial populations around a growth-modulating threshold via analysis of the effect of non-genetic inheritance, similar to conditions that create antibiotic-tolerant persister cells and other examples of bet hedging. Using simulations and experimental lineage data in Escherichia coli, we present evidence that regulation of growth amplifies the dependence of growth arrest on cellular lineage, causing clusters of related cells undergo growth arrest in certain conditions. Our simulations predict that lineage correlations and the sensitivity of growth to changes in toxin levels coincide in a critical regime. Below the critical regime, the sizes of related growth arrested clusters are distributed exponentially, while in the critical regime clusters sizes are more likely to become large. Furthermore, phenotypic diversity can be nearly as high as possible near the critical regime, but for most parameter values it falls far below the theoretical limit. We conclude that lineage information is indispensable for understanding regulation of cellular growth.

PMID: 30133447 [PubMed - indexed for MEDLINE]

Crosstalk and the evolvability of intracellular communication.

Wed, 12/12/2018 - 05:05
Related Articles

Crosstalk and the evolvability of intracellular communication.

Nat Commun. 2017 07 10;8:16009

Authors: Rowland MA, Greenbaum JM, Deeds EJ

Abstract
Metazoan signalling networks are complex, with extensive crosstalk between pathways. It is unclear what pressures drove the evolution of this architecture. We explore the hypothesis that crosstalk allows different cell types, each expressing a specific subset of signalling proteins, to activate different outputs when faced with the same inputs, responding differently to the same environment. We find that the pressure to generate diversity leads to the evolution of networks with extensive crosstalk. Using available data, we find that human tissues exhibit higher levels of diversity between cell types than networks with random expression patterns or networks with no crosstalk. We also find that crosstalk and differential expression can influence drug activity: no protein has the same impact on two tissues when inhibited. In addition to providing a possible explanation for the evolution of crosstalk, our work indicates that consideration of cellular context will likely be crucial for targeting signalling networks.

PMID: 28691706 [PubMed - indexed for MEDLINE]

Gene ontology improves template selection in comparative protein docking.

Fri, 12/07/2018 - 10:05
Related Articles

Gene ontology improves template selection in comparative protein docking.

Proteins. 2018 Dec 06;:

Authors: Hadarovich A, Anishchenko I, Tuzikov AV, Kundrotas PJ, Vakser IA

Abstract
Structural characterization of protein-protein interactions is essential for our ability to study life processes at the molecular level. Computational modeling of protein complexes (protein docking) is important as the source of their structure, and as a way to understand the principles of protein interaction. Rapidly evolving comparative docking approaches utilize target/template similarity metrics, which are often based on the protein structure. Although the structural similarity, generally, yields good performance, other characteristics of the interacting proteins (eg, function, biological process, localization, and such) may improve the prediction quality, especially in the case of weak target/template structural similarity. For the ranking of a pool of models for each target, we tested scoring functions that quantify similarity of Gene Ontology (GO) terms assigned to target and template proteins in three ontology domains - biological process, molecular function and cellular component (GO-score). The scoring functions were tested in docking of bound, unbound and modeled proteins. The results indicate that the combined structural and GO-terms functions improve the scoring, especially in the twilight zone of structural similarity, typical for protein models of limited accuracy. This article is protected by copyright. All rights reserved.

PMID: 30520123 [PubMed - as supplied by publisher]

Evolutionary pathways of repeat protein topology in bacterial outer membrane proteins.

Fri, 11/30/2018 - 10:17

Evolutionary pathways of repeat protein topology in bacterial outer membrane proteins.

Elife. 2018 Nov 29;7:

Authors: Franklin MW, Nepomnyachyi S, Feehan R, Ben-Tal N, Kolodny R, Slusky JS

Abstract
Outer membrane proteins (OMPs) are the proteins in the surface of Gram-negative bacteria. These proteins have diverse functions but a single topology: the β-barrel. Sequence analysis has suggested that this common fold is a β-hairpin repeat protein, and that amplification of the β-hairpin has resulted in 8-26-stranded barrels. Using an integrated approach that combines sequence and structural analyses we find events in which non-amplification diversification also increases barrel strand number. Our network-based analysis reveals strand-number evolutionary pathways, including one that progresses from a primordial 8-stranded barrel to 16-strands and further, to 18-strands. Among these are mechanisms of strand number accretion without domain duplication, like a loop-to-hairpin transition. These mechanisms illustrate perpetuation of repeat protein topology without genetic duplication, likely induced by the hydrophobic membrane. Finally, we find that the evolutionary trace is particularly prominent in the C-terminal half of OMPs, implicating this region in the nucleation of OMP folding.

PMID: 30489257 [PubMed - as supplied by publisher]


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