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Varun Mandalaparthy, Venkata Ramana Sanaboyana, Hitesh Rafalia, Shachi Gosavi
One of the main barriers to accurate computational protein structure prediction is searching the vast space of protein conformations. Distance restraints or inter-residue contacts have been used to reduce this search space, easing the discovery of the correct folded state. It has been suggested that about one contact for every twelve residues may be sufficient to predict structure at fold level accuracy. Here, we use coarse-grained structure-based models in conjunction with molecular dynamics simulations to examine this empirical prediction...
December 3, 2017: Proteins
Wei-Lin Hsu, Tadaomi Furuta, Minoru Sakurai
The Escherichia coli maltose transporter MalFGK2 -E belongs to the protein superfamily of ATP-binding cassette (ABC) transporters. This protein is composed of heterodimeric transmembrane domains (TMDs) MalF and MalG, and the homodimeric nucleotide-binding domains (NBDs) MalK2 . In addition to the TMDs and NBDs, the periplasmic maltose binding protein MalE captures maltose and shuttle it to the transporter. In this study, we performed all-atom molecular dynamics (MD) simulations on the maltose transporter and found that both the binding of MalE to the periplasmic side of the TMDs and binding of ATP to the MalK2 are necessary to facilitate the conformational change from the inward-facing state to the occluded state, in which MalK2 is completely dimerized...
December 1, 2017: Proteins
B Kesavan, A Arockiasamy, Krishnaswamy Sankaran
The lytic enzyme, endolysin, is encoded by bacteriophages (phages) to destroy the peptidoglycan layer of host bacterial cells. The release of phage progenies to start the new infection cycle is dependent on the cell lysis event. Endolysin encoded by DLP12 cryptic prophage is a SAR endolysin which is retained by the bacterium presumably due to the benefit it confers. The structure of DLP12 endolysin (Id: 4ZPU) determined at 2.4Å resolution is presented here. The DLP12 endolysin structure shows a modular nature and is organized into distinct structural regions...
November 27, 2017: Proteins
Yosef Y Kuttner, Stanislav Engel
A rational design of protein complexes with defined functionalities and of drugs aimed at disrupting protein-protein interactions requires fundamental understanding of the mechanisms underlying the formation of specific protein complexes. Efforts to develop efficient small-molecule or protein-based binders often exploit energetic hot spots on protein surfaces, namely, the interfacial residues that provide most of the binding free energy in the complex. The molecular basis underlying the unusually high energy contribution of the hot spots remains obscure, and its elucidation can facilitate the design of interface-targeted drugs...
November 27, 2017: Proteins
Peter B Chi, Dohyup Kim, Jason K Lai, Nadia Bykova, Claudia C Weber, Jan Kubelka, David A Liberles
Improvements in the description of amino acid substitution are required to develop better pseudo-energy-based protein structure-aware models for use in phylogenetic studies. These models are used to characterize the probabilities of amino acid substitution and enable better simulation of protein sequences over a phylogeny. A better characterization of amino acid substitution probabilities in turn enables numerous downstream applications, like detecting positive selection, ancestral sequence reconstruction, and evolutionarily-motivated protein engineering...
November 27, 2017: Proteins
Tsukasa Nakamura, Toshiyuki Oda, Yoshinori Fukasawa, Kentaro Tomii
Proteins often exist as their multimeric forms when they function as so-called biological assemblies consisting of the specific number and arrangement of protein subunits. Consequently, elucidating biological assemblies is necessary to improve understanding of protein function. Template-Based Modeling (TBM), based on known protein structures, has been used widely for protein structure prediction. Actually, TBM has become an increasingly useful approach in recent years because of the increased amounts of information related to protein amino acid sequences and three-dimensional structures...
November 27, 2017: Proteins
Jürgen Haas, Alessandro Barbato, Dario Behringer, Gabriel Studer, Steven Roth, Martino Bertoni, Khaled Mostaguir, Rafal Gumienny, Torsten Schwede
Every second year, the community experiment "Critical Assessment of Techniques for Structure Prediction" (CASP) is conducting an independent blind assessment of structure prediction methods, providing a framework for comparing the performance of different approaches and discussing the latest developments in the field. Yet, developers of automated computational modeling methods clearly benefit from more frequent evaluations based on larger sets of data. The "Continuous Automated Model EvaluatiOn (CAMEO)" platform complements the CASP experiment by conducting fully automated blind prediction assessments based on the weekly pre-release of sequences of those structures, which are going to be published in the next release of the PDB Protein Data Bank...
November 27, 2017: Proteins
Andriy Kryshtafovych, Bohdan Monastyrskyy, Krzysztof Fidelis, John Moult, Torsten Schwede, Anna Tramontano
The paper describes results of numerical evaluation of CASP12 models submitted on targets for which structural templates could be identified and for which servers produced models of relatively high accuracy. The emphasis is on analysis of details of models, and how well the models compete with experimental structures. Performance of contributing research groups is measured in terms of backbone accuracy, all-atom local geometry, and the ability to estimate local errors in models. Separate analyses for all participating groups and automatic servers were carried out...
November 21, 2017: Proteins
Seung Hwan Hong, InSuk Joung, Jose C Flores-Canales, Balachandran Manavalan, Qianyi Cheng, Seungryong Heo, Jong Yun Kim, Sun Young Lee, Mikyung Nam, Keehyoung Joo, In-Ho Lee, Sung Jong Lee, Jooyoung Lee
For protein structure modeling in the CASP12 experiment, we have developed a new protocol based on our previous CASP11 approach. The global optimization method of conformational space annealing (CSA) was applied to three stages of modeling: multiple sequence-structure alignment, three-dimensional (3D) chain building, and side-chain re-modeling. For better template selection and model selection, we updated our model quality assessment (QA) method with the newly developed SVMQA (support vector machine for quality assessment)...
November 21, 2017: Proteins
Guennadi Kozlov, Kathy Wong, Kalle Gehring
Legionella pneumophila is a pathogen causing severe pneumonia in humans called Legionnaires' disease. Lem22 is a previously uncharacterized effector protein conserved in multiple Legionella strains. Here, we report the crystal structure of Lem22 from the Philadelphia strain, also known as lpg2328, at 1.40 Å resolution. The structure shows an up-and-down three-helical bundle with a significant structural similarity to a number of protein-binding domains involved in apoptosis and membrane trafficking. Sequence conservation identifies a putative functional site on the interface of helices 2 and 3...
November 21, 2017: Proteins
Clyde L Denis, Roy Richardson, Shiwha Park, Chongxu Zhang, Wen Xi, Thomas M Laue, Xin Wang
The eukaryotic eRF1 translation termination factor plays an important role in recognizing stop codons and initiating the end to translation. However, which exact complexes contain eRF1 and at what abundance is not clear. We have used analytical ultracentrifugation with fluorescent detection system to identify the protein complexome of eRF1 in the yeast Saccharomyces cerevisiae. In addition to eRF1 presence in translating polysomes, we found that eRF1 associated with five other macromolecular complexes: 77S, 57S, 39S, 28S, and 20S in size...
November 15, 2017: Proteins
Luciano A Abriata, Giorgio E Tamò, Bohdan Monastyrskyy, Andriy Kryshtafovych, Matteo Dal Peraro
We present our assessment of CASP12 modeling efforts for targets with no obvious templates of high sequence/structure similarity in the PDB, i.e. for evaluation units of the free modeling (FM) and free modeling/template-based modeling (FM/TBM) categories. Models were clustered and ranked using the Global Distance Test-Total Score and five additional metrics developed in previous CASP rounds, producing short lists of models that were subject to visual inspection in comparison to the target structures. The whole procedure was implemented as a web app that facilitates model selection and visual inspection, and could become useful to facilitate and standardize future assessments...
November 15, 2017: Proteins
Akshay Bhatnagar, Debashree Bandyopadhyay
We have demonstrated earlier that protein microenvironments were conserved around disulphide-bridged cystine motifs with similar functions, irrespective of diversity in protein sequences (Bhatnagar et al., 2016; 84:1576-1589) . Here, cysteine thiol modifications were characterized based on protein microenvironments, secondary structures and specific protein functions. Protein microenvironment around an amino acid was defined as the summation of hydrophobic contributions from the surrounding protein fragments and the solvent molecules present within its first contact shell (Bandyopadhyay and Mehler, Proteins 2008; 72:646-659)...
November 15, 2017: Proteins
Agnieszka S Karczyńska, Magdalena A Mozolewska, Paweƚ Krupa, Artur Gieƚdoń, Adam Liwo, Cezary Czaplewski
A new approach to assisted protein-structure prediction has been proposed, which is based on running multiplexed replica exchange molecular dynamics simulations with the coarse-grained UNRES force field with restraints derived from knowledge-based models and distance distribution from small angle X-ray scattering (SAXS) measurements. The latter restraints are incorporated into the target function as a maximum-likelihood term that guides the shape of the simulated structures towards that defined by SAXS. The approach was first verified with the 1KOY protein, for which the distance distribution was calculated from the experimental structure, and subsequently used to predict the structures of 11 data-assisted targets in the CASP12 experiment...
November 14, 2017: Proteins
Marissa A McKercher, Xiaoyang Guan, Zhongping Tan, Deborah S Wuttke
SH2B1 is a multidomain protein that serves as a key adapter to regulate numerous cellular events, such as insulin, leptin, and growth hormone signaling pathways. Many of these protein-protein interactions are mediated by the SH2 domain of SH2B1, which recognizes ligands containing a phosphorylated tyrosine (pY), including peptides derived from janus kinase 2, insulin receptor, and insulin receptor substrate-1 and -2. Specificity for the SH2 domain of SH2B1 is conferred in these ligands either a hydrophobic or an acidic side chain at the +3 position C-terminal to the pY...
November 11, 2017: Proteins
Marc F Lensink, Sameer Velankar, Minkyung Baek, Lim Heo, Chaok Seok, Shoshana J Wodak
We present the quality assessment of 5613 models submitted by predictor groups from both CAPRI and CASP for the total of 15 most tractable targets from the second joint CASP-CAPRI protein assembly prediction experiment. These targets comprised 12 homo-oligomers and 3 hetero-complexes. The bulk of the analysis focuses on 10 targets (of CAPRI Round 37), which included all 3 hetero-complexes, and whose protein chains or the full assembly could be readily modeled from structural templates in the PDB. On average, 28 CAPRI groups and 10 CASP groups (including automatic servers), submitted models for each of these 10 targets...
November 10, 2017: Proteins
Guang Song
In this work, we carry out a comparative study of the homo 360-mer structures of viral capsids and bacterial micro-compartments (MCPs). Different from viral 360-mers that all are arranged on a skewed right-handed icosahedral lattice with a triangulation number T of 7, the new 360-mer structure of AaLS-13, an engineered bacterial micro-compartment, offers a novel open conformation that has a unique unskewed lattice arrangement with a triangulation number T of 1 and large keyhole-shaped pores in the shell. By comparing their differences, we are able to predict a closed conformation of AaLS-13 that has the same lattice arrangement as existing viral capsid structures and in which all the keyhole-shaped pores are shut...
November 7, 2017: Proteins
Ahmet Sureyya Rifaioglu, Tunca Doğan, Ömer Sinan Saraç, Tulin Ersahin, Rabie Saidi, Mehmet Volkan Atalay, Maria Jesus Martin, Rengul Cetin-Atalay
Recent advances in computing power and machine learning empower functional annotation of protein sequences and their transcript variations. Here, we present an automated prediction system UniGOPred, for GO annotations and a database of GO term predictions for proteomes of several organisms in UniProt Knowledgebase (UniProtKB). UniGOPred provides function predictions for 514 molecular function (MF), 2909 biological process (BP) and 438 cellular component (CC) GO terms for each protein sequence. UniGOPred covers nearly the whole functionality spectrum in Gene Ontology system and it can predict both generic and specific GO terms...
November 3, 2017: Proteins
John Moult, Krzysztof Fidelis, Andriy Kryshtafovych, Torsten Schwede, Anna Tramontano
This paper reports the outcome of the 12th round of Critical Assessment of Structure Prediction (CASP12), held in 2016. CASP is a community experiment to determine the state of the art in modeling protein structure from amino acid sequence. Participants are provided sequence information and in turn provide protein structure models and related information. Analysis of the submitted structures by independent assessors provides a comprehensive picture of the capabilities of current methods, and allows progress to be identified...
October 30, 2017: Proteins
Samiul M Ansari, Jesper Sørensen, Birgit Schiøtt, David S Palmer
Bovine and camel chymosins are aspartic proteases that are used in dairy food manufacturing. Both enzymes catalyse proteolysis of a milk protein, κ-casein, which helps to initiate milk coagulation. Surprisingly, camel chymosin shows a 70% higher clotting activity than bovine chymosin for bovine milk, while exhibiting only 20% of the unspecific proteolytic activity. By contrast, bovine chymosin is a poor coagulant for camel milk. Although both enzymes are marketed commercially, the disparity in their catalytic activity is not yet well understood at a molecular level, due in part to a lack of atomistic resolution data about the chymosin - κ-casein complexes...
October 30, 2017: Proteins
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