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Badri Adhikari, Jie Hou, Jianlin Cheng
In this work, we report the evaluation of the residue-residue contacts predicted by our three different methods in the CASP12 experiment, focusing on studying the impact of multiple sequence alignment, residue coevolution and machine learning on contact prediction. The first method (MULTICOM-NOVEL) uses only traditional features (sequence profile, secondary structure and solvent accessibility) with deep learning to predict contacts and serves as a baseline. The second method (MULTICOM-CONSTRUCT) uses our new alignment algorithm to generate deep multiple sequence alignment to derive coevolution-based features, which are integrated by a neural network method to predict contacts...
October 19, 2017: Proteins
Gyu Rie Lee, Lim Heo, Chaok Seok
Advances in protein model refinement techniques are required as diverse sources of protein structure information are available from low-resolution experiments or informatics-based computations such as cryo-EM, NMR, homology models, or predicted residue contacts. Given semi-reliable or incomplete structural information, structure quality of a protein model has to be improved by ab initio methods such as energy-based simulation. In this study, we describe a new automatic refinement server method designed to improve locally inaccurate regions and overall structure simultaneously...
October 16, 2017: Proteins
Julia Koehler Leman, Andrew R D'Avino, Yash Bhatnagar, Jeffrey J Gray
Membrane proteins are challenging to study and restraints for structure determination are typically sparse or of low resolution because the membrane environment that surrounds them leads to a variety of experimental challenges. When membrane protein structures are determined by different techniques in different environments, a natural question is "which structure is most biologically relevant?" Towards answering this question, we compiled a dataset of membrane proteins with known structures determined by both solution NMR and X-ray crystallography...
October 16, 2017: Proteins
Luciano A Abriata, Lisa N Kinch, Giorgio E Tamò, Bohdan Monastyrskyy, Andriy Kryshtafovych, Matteo Dal Peraro
For assessment purposes, CASP targets are split into evaluation units. We herein present the official definition of CASP12 evaluation units (EUs) and their classification into difficulty categories. Each target can be evaluated as one EU (the whole target) or/and several EUs (separate structural domains or groups of structural domains). The specific scenario for a target split is determined by the domain organization of available templates, the difference in server performance on separate domains versus combination of the domains, and visual inspection...
October 16, 2017: Proteins
Magda Toda, Fangyuan Zhang, Bhagya Athukorallage
Over the past two decades, many different geometric models were created for beta barrels, including, but not limited to: cylinders, one sheeted hyperboloids, twisted hyperboloids, catenoids etc. We are proponents of an elastic surface model for beta-barrels, which includes the minimal surface model as a particular case, but is a lot more comprehensive. Beta barrel models are obtained as numerical solutions of a boundary value problem, using the COMSOL Multiphysics Modeling Software. We have compared them against the best fitting statistical models, with positive results...
October 12, 2017: Proteins
Danfeng Shi, Qifeng Bai, Shuangyan Zhou, Xuewei Liu, Huanxiang Liu, Xiaojun Yao
As co-chaperones of the 90-kDa heat shock protein(HSP90), FK506 binding protein 51 (FKBP51) and FK506 binding protein 52 (FKBP52) modulate the maturation of steroid hormone receptor through their specific FK1 domains (FKBP12-like domain 1). The inhibitors targeting FK1 domains are potential therapies for endocrine-related physiological disorders. However, the structural conservation of the FK1 domains between FKBP51 and FKBP52 make it difficult to obtain satisfactory selectivity in FK506-based drug design. Fortunately, a series of iFit ligands synthesized by Hausch et al exhibited excellent selectivity for FKBP51, providing new opportunity for design selective inhibitors...
October 12, 2017: Proteins
Mutyala Satish, M Angel Nivya, Suman Abhishek, Naveen Kumar Nakarakanti, Dixit Shivani, M Vinuthna Vani, Eerappa Rajakumara
Histone lysine methylation by histone lysine methyltransferases (HKMTs) has been implicated in regulation of gene expression. While significant progress has been made to understand the roles and mechanisms of animal HKMT functions, only a few plant HKMTs are functionally characterized. To unravel histone substrate specificity, degree of methylation and catalytic activity, we analysed ATX, SUVH, SUVR, ATXR5, ATXR6, and E(Z) HKMTs of Arabidopsis, maize and rice through sequence and structure comparison. We show that ATXs may exhibit methyltransferase specificity towards histone 3 lysine 4 (H3K4) and might catalyse the tri-methylation...
October 11, 2017: Proteins
Jimin Park, Hyojin Kim, Suwon Kim, Daeun Lee, Mi-Sun Kim, Dong Hae Shin
The crystal structure of HldC from B. pseudomallei (BpHldC), the fourth enzyme of the heptose biosynthesis pathway, has been determined. BpHldC converts ATP and d-glycero-β-d-manno-heptose-1-phosphate into ADP-d-glycero-β -d-manno-heptose and pyrophosphate. The crystal structure of BpHldC belongs to the nucleotidyltransferase α/β phosphodiesterase superfamily sharing a common Rossmann-like α/β fold with a conserved T/HXGH sequence motif. The invariant catalytic key residues of BpHldC indicate that the core catalytic mechanism of BpHldC may be similar to that of other closest homologues...
October 7, 2017: Proteins
D A Karasev, D A Veselova, A V Veselovsky, B N Sobolev, V G Zgoda, A I Archakov
Protein phosphorylation is widely used in biological regulatory processes. The study of spatial features related to phosphorylation sites is necessary to increase the efficacy of recognition of phosphorylation patterns in protein sequences. Using the data on phosphosites found in amino acid sequences, we mapped these sites onto 3D structures and studied the structural variability of the same sites in different PDB entries related to the same proteins. Solvent accessibility was calculated for the residues known to be phosphorylated...
October 7, 2017: Proteins
Tianyun Liu, Shirbi Ish-Shalom, Wen Torng, Aleix Lafita, Christian Bock, Matthew Mort, David N Cooper, Spencer Bliven, Guido Capitani, Sean D Mooney, Russ B Altman
Our goal is to answer the question: compared with experimental structures, how useful are predicted models for functional annotation? We assessed the functional utility of predicted models by comparing the performances of a suite of methods for functional characterization on the predictions and the experimental structures. We identified 28 sites in 25 protein targets to perform functional assessment. These 28 sites included nine sites with known ligand binding (holo-sites), nine sites that are expected or suggested by experimental authors for small molecule binding (apo-sites), and ten sites containing important motifs, loops, or key residues with important disease-associated mutations...
October 4, 2017: Proteins
Lim Heo, Michael Feig
Protein structure refinement remains a challenging yet important problem as it has the potential to bring already accurate template-based models to near-native resolution. Refinement based on molecular dynamics simulations has been a highly promising approach and the performance of MD-based refinement in the Feig group during CASP12 is described here. During CASP12, sampling was extended well into the microsecond scale, an improved force field was applied, and new protocol variations were tested. Progress over previous rounds of CASP was found to be limited which is analyzed in terms of the quality of the initial models and dependency on the amount of sampling and refinement protocol variations...
October 4, 2017: Proteins
Arne Elofsson, Keehyoung Joo, Chen Keasar, Jooyoung Lee, Ali H A Maghrabi, Balachandran Manavalan, Liam J McGuffin, David Ménendez Hurtado, Claudio Mirabello, Robert Pilstål, Tomer Sidi, Karolis Uziela, Björn Wallner
Methods to reliably estimate the quality of 3D models of proteins are essential drivers for the wide adoption and serious acceptance of protein structure predictions by life scientists. In this paper, the most successful groups in CASP12 describe their latest methods for Estimates of Model Accuracy (EMA). We show that pure single model accuracy estimation methods have shown clear progress since CASP11; the three top methods (MESHI, ProQ3, SVMQA) all perform better than the top method of CASP11 (ProQ2). While the pure single model accuracy estimation methods outperform quasi-single (ModFOLD6 variations) and consensus methods (Pcons, ModFOLDclust2, Pcomb-domain and Wallner) in model selection, they are still not as good as those methods in absolute model quality estimation and predictions of local quality...
October 4, 2017: Proteins
Patrick Slama
Residues at different positions of a multiple sequence alignment sometimes evolve together, due to a correlated structural or functional stress at these positions. Co-evolution has thus been evidenced computationally in multiple proteins or protein domains. Here, we wish to study whether an evolutionary stress is exerted on a sequence alignment across protein domains, i.e., on longer sequence separations than within a single protein domain. JmjC-containing lysine demethylases were chosen for analysis, as a follow-up to previous studies; these proteins are important multi-domain epigenetic regulators...
October 4, 2017: Proteins
Andriy Kryshtafovych, Reinhard Albrecht, Arnaud Baslé, Pedro Bule, Alessandro T Caputo, Ana Luisa Carvalho, Kinlin L Chao, Ron Diskin, Krzysztof Fidelis, Carlos M G A Fontes, Folmer Fredslund, Harry J Gilbert, Celia W Goulding, Marcus D Hartmann, Christopher S Hayes, Osnat Herzberg, Johan C Hill, Andrzej Joachimiak, Gert-Wieland Kohring, Roman I Koning, Leila Lo Leggio, Marco Mangiagalli, Karolina Michalska, John Moult, Shabir Najmudin, Marco Nardini, Valentina Nardone, Didier Ndeh, Thanh H Nguyen, Guido Pintacuda, Sandra Postel, Mark J van Raaij, Pietro Roversi, Amir Shimon, Abhimanyu K Singh, Eric J Sundberg, Kaspars Tars, Nicole Zitzmann, Torsten Schwede
The functional and biological significance of the selected CASP12 targets are described by the authors of the structures. The crystallographers discuss the most interesting structural features of the target proteins and assess whether these features were correctly reproduced in the predictions submitted to the CASP12 experiment. This article is protected by copyright. All rights reserved.
September 28, 2017: Proteins
Sergey Ovchinnikov, Hahnbeom Park, David Kim, Frank DiMaio, David Baker
We describe several notable aspects of our structure predictions using Rosetta in CASP12 in the free modeling (FM) and refinement (TR) categories. First, we had previously generated (and published) models for most large protein families lacking experimentally determined structures using Rosetta guided by co-evolution based contact predictions, and for several targets these models proved better starting points for comparative modeling than any known crystal structure-our model database thus starts to fulfill one of the goals of the original protein structure initiative...
September 22, 2017: Proteins
Venkata N Are, Sahayog N Jamdar, Biplab Ghosh, Venuka Durani Goyal, Ashwani Kumar, Sanchit Neema, Rekha Gadre, Ravindra D Makde
Xaa-Pro peptidases (XPP) are dinuclear peptidases of MEROPS M24B family that hydrolyze Xaa-Pro iminopeptide bond with a trans-proline at the second position of the peptide substrate. XPPs specific towards dipeptides are called prolidases while those that prefer longer oligopeptides are called aminopeptidases P. Though XPPs are strictly conserved in bacterial and archaeal species, the structural and sequence features that distinguish between prolidases and aminopeptidases P are not always clear. Here, we report 1...
September 20, 2017: Proteins
Xue Wang, Min Li Xu, Bao Qiong Li, Hong Lin Zhai, Jin Jin Liu, Shuyan Li
Protein phosphorylation is one of the most pervasive post-translational modifications and regulates diverse cellular processes in organisms. Under the catalysis of protein kinases, protein phosphorylation usually occurred in the residues serine (S), threonine (T) or tyrosine (Y). In this contribution, we proposed a novel scheme (named KMPhos) for the theoretical prediction of protein phosphorylation sites. First, the numerical matrix was obtained from a protein sequence fragment by replacing the characters of the residues with the chemical descriptors of amino acid molecules to approximately describe the chemical environment of the protein fragment, which was turned to the grayscale image...
September 18, 2017: Proteins
Hahnbeom Park, David Kim, Sergey Ovchinnikov, David Baker, Frank DiMaio
Many naturally occurring protein systems function primarily as symmetric assemblies. Prediction of the quaternary structure of these assemblies is an important biological problem. This manuscript describes automated tools we have developed for predicting the structure of symmetric protein assemblies in the Robetta structure prediction server. We assess the performance of this pipeline on a set of targets from the recent CASP12/CAPRI blind quaternary structure prediction experiment. Our approach successfully predicted five of seven symmetric assemblies in this challenge, and was assessed as the best participating server group, and one of only two groups (human or server) with two predictions judged as high quality by the assessors...
September 14, 2017: Proteins
Youichi Naoe, Nozomi Nakamura, Md Mahfuzur Rahman, Takehiko Tosha, Satoru Nagatoishi, Kouhei Tsumoto, Yoshitsugu Shiro, Hiroshi Sugimoto
Periplasmic heme-binding proteins (PBPs) in Gram-negative bacteria are components of the heme acquisition system. These proteins shuttle heme across the periplasmic space from outer membrane receptors to ATP-binding cassette (ABC) heme importers located in the inner-membrane. In the present study, we characterized the structures of PBPs found in the pathogen Burkholderia cenocepacia (BhuT) and in the thermophile Roseiflexus sp. RS-1 (RhuT) in the heme-free and heme-bound forms. The conserved motif, in which a well-conserved Tyr interacts with the nearby Arg coordinates on heme iron, was observed in both PBPs...
September 14, 2017: Proteins
Justas Dapkūnas, Kliment Olechnovič, Česlovas Venclovas
We participated in CAPRI Round 37, held jointly with CASP12, having two major objectives. First, we intended to test the utility of our PPI3D web server in finding and selecting templates for comparative modeling of structures of protein complexes. Our second aim was to evaluate the ability of our model accuracy estimation method VoroMQA to score and rank structural models for protein-protein interactions. Using sequence search in PPI3D and HHpred servers we identified multimeric templates for 7 of 11 CAPRI targets, and models of at least acceptable quality were constructed for 6 of them...
September 14, 2017: Proteins
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