Protein Structure Prediction by Protein Alignments
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Structural Analysis of 3′Utrs in Insect Flaviviruses
bioRxiv preprint doi: https://doi.org/10.1101/2021.06.23.449515; this version posted June 24, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Structural analysis of 3’UTRs in insect flaviviruses reveals novel determinant of sfRNA biogenesis and provides new insights into flavivirus evolution Andrii Slonchak1,#, Rhys Parry1, Brody Pullinger1, Julian D.J. Sng1, Xiaohui Wang1, Teresa F Buck1,2, Francisco J Torres1, Jessica J Harrison1, Agathe M G Colmant1, Jody Hobson- Peters1,3, Roy A Hall1,3, Andrew Tuplin4, Alexander A Khromykh1,3,# 1 School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD, Australia 2Current affiliation: Institute for Medical and Marine Biotechnology, University of Lübeck, Lübeck, Germany 3Australian Infectious Diseases Research Centre, Global Virus Network Centre of Excellence, Brisbane, QLD, Australia 4 School of Molecular and Cellular Biology, University of Leeds, Leeds, U.K. # corresponding authors: [email protected]; [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.06.23.449515; this version posted June 24, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Insect-specific flaviviruses (ISFs) circulate in nature due to vertical transmission in mosquitoes and do not infect vertebrates. ISFs include two distinct lineages – classical ISFs (cISFs) that evolved independently and dual host associated ISFs (dISFs) that are proposed to diverge from mosquito-borne flaviviruses (MBFs). Compared to pathogenic flaviviruses, ISFs are relatively poorly studied, and their molecular biology remains largely unexplored. -
Giri Narasimhan ECS 254A; Phone: X3748 [email protected] July 2011
BSC 4934: QʼBIC Capstone Workshop" Giri Narasimhan ECS 254A; Phone: x3748 [email protected] http://www.cs.fiu.edu/~giri/teach/BSC4934_Su11.html July 2011 7/19/11 Q'BIC Bioinformatics 1 Modular Nature of Proteins" Proteins# are collections of “modular” domains. For example, Coagulation Factor XII F2 E F2 E K Catalytic Domain F2 E K K Catalytic Domain PLAT 7/21/10 Modular Nature of Protein Structures" Example: Diphtheria Toxin 7/21/10 Domain Architecture Tools" CDART# " #Protein AAH24495; Domain Architecture; " #It’s domain relatives; " #Multiple alignment for 2nd domain SMART# 7/21/10 Active Sites" Active sites in proteins are usually hydrophobic pockets/ crevices/troughs that involve sidechain atoms. 7/21/10 Active Sites" Left PDB 3RTD (streptavidin) and the first site located by the MOE Site Finder. Middle 3RTD with complexed ligand (biotin). Right Biotin ligand overlaid with calculated alpha spheres of the first site. 7/21/10 Secondary Structure Prediction Software" 7/21/10 PDB: Protein Data Bank" #Database of protein tertiary and quaternary structures and protein complexes. http:// www.rcsb.org/pdb/ #Over 29,000 structures as of Feb 1, 2005. #Structures determined by " # NMR Spectroscopy " # X-ray crystallography " # Computational prediction methods #Sample PDB file: Click here [▪] 7/21/10 Protein Folding" Unfolded Rapid (< 1s) Molten Globule State Slow (1 – 1000 s) Folded Native State #How to find minimum energy configuration? 7/21/10 Protein Structures" #Most proteins have a hydrophobic core. #Within the core, specific interactions take place between amino acid side chains. #Can an amino acid be replaced by some other amino acid? " # Limited by space and available contacts with nearby amino acids #Outside the core, proteins are composed of loops and structural elements in contact with water, solvent, other proteins and other structures. -
Estimation of Uncertainties in the Global Distance Test (GDT TS) for CASP Models
RESEARCH ARTICLE Estimation of Uncertainties in the Global Distance Test (GDT_TS) for CASP Models Wenlin Li2, R. Dustin Schaeffer1, Zbyszek Otwinowski2, Nick V. Grishin1,2* 1 Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas, 75390–9050, United States of America, 2 Department of Biochemistry and Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, Texas, 75390–9050, United States of America * [email protected] Abstract a11111 The Critical Assessment of techniques for protein Structure Prediction (or CASP) is a com- munity-wide blind test experiment to reveal the best accomplishments of structure model- ing. Assessors have been using the Global Distance Test (GDT_TS) measure to quantify prediction performance since CASP3 in 1998. However, identifying significant score differ- ences between close models is difficult because of the lack of uncertainty estimations for OPEN ACCESS this measure. Here, we utilized the atomic fluctuations caused by structure flexibility to esti- Citation: Li W, Schaeffer RD, Otwinowski Z, Grishin mate the uncertainty of GDT_TS scores. Structures determined by nuclear magnetic reso- NV (2016) Estimation of Uncertainties in the Global nance are deposited as ensembles of alternative conformers that reflect the structural Distance Test (GDT_TS) for CASP Models. PLoS flexibility, whereas standard X-ray refinement produces the static structure averaged over ONE 11(5): e0154786. doi:10.1371/journal. time and space for the dynamic ensembles. To recapitulate the structural heterogeneous pone.0154786 ensemble in the crystal lattice, we performed time-averaged refinement for X-ray datasets Editor: Yang Zhang, University of Michigan, UNITED to generate structural ensembles for our GDT_TS uncertainty analysis. -
Methods for the Refinement of Protein Structure 3D Models
International Journal of Molecular Sciences Review Methods for the Refinement of Protein Structure 3D Models Recep Adiyaman and Liam James McGuffin * School of Biological Sciences, University of Reading, Reading RG6 6AS, UK; [email protected] * Correspondence: l.j.mcguffi[email protected]; Tel.: +44-0-118-378-6332 Received: 2 April 2019; Accepted: 7 May 2019; Published: 1 May 2019 Abstract: The refinement of predicted 3D protein models is crucial in bringing them closer towards experimental accuracy for further computational studies. Refinement approaches can be divided into two main stages: The sampling and scoring stages. Sampling strategies, such as the popular Molecular Dynamics (MD)-based protocols, aim to generate improved 3D models. However, generating 3D models that are closer to the native structure than the initial model remains challenging, as structural deviations from the native basin can be encountered due to force-field inaccuracies. Therefore, different restraint strategies have been applied in order to avoid deviations away from the native structure. For example, the accurate prediction of local errors and/or contacts in the initial models can be used to guide restraints. MD-based protocols, using physics-based force fields and smart restraints, have made significant progress towards a more consistent refinement of 3D models. The scoring stage, including energy functions and Model Quality Assessment Programs (MQAPs) are also used to discriminate near-native conformations from non-native conformations. Nevertheless, there are often very small differences among generated 3D models in refinement pipelines, which makes model discrimination and selection problematic. For this reason, the identification of the most native-like conformations remains a major challenge. -
Advances and Pitfalls of Protein Structural Alignment Hitomi Hasegawa1 and Liisa Holm1,2
Available online at www.sciencedirect.com Advances and pitfalls of protein structural alignment Hitomi Hasegawa1 and Liisa Holm1,2 Structure comparison opens a window into the distant past of illustrated in a review [1]. Visual recognition of recurrent protein evolution, which has been unreachable by sequence folding patterns between unrelated proteins suggested comparison alone. With 55 000 entries in the Protein Data Bank that there might exist a finite number of admissible folds. and about 500 new structures added each week, automated Hierarchical taxonomies of protein structures were pro- processing, comparison, and classification are necessary. A posed wherein clusters of homologous proteins are nested variety of methods use different representations, scoring within folds, and every fold is slotted into one of four functions, and optimization algorithms, and they generate classes. Automated clusterings were generated, which contradictory results even for moderately distant structures. were in broad general agreement with manual and semi- Sequence mutations, insertions, and deletions are automated classifications. Lately, the hierarchical view accommodated by plastic deformations of the common core, with discrete folds has given way to a view where related retaining the precise geometry of the active site, and peripheral structures form elongated clusters in fold space and folds regions may refold completely. Therefore structure comparison can be morphed continuously one into another [2,3]. methods that allow for flexibility and plasticity generate the most biologically meaningful alignments. Active research There is no universally acknowledged definition of what directions include both the search for fold invariant features and constitutes structural similarity but we all know it when the modeling of structural transitions in evolution. -
Design and Applications of a Clamp for Green Fluorescent Protein with Picomolar Afnity Received: 22 August 2017 Simon Hansen1,2, Jakob C
www.nature.com/scientificreports OPEN Design and applications of a clamp for Green Fluorescent Protein with picomolar afnity Received: 22 August 2017 Simon Hansen1,2, Jakob C. Stüber 1, Patrick Ernst1, Alexander Koch1, Daniel Bojar1,3, Accepted: 31 October 2017 Alexander Batyuk 1,4 & Andreas Plückthun 1 Published: xx xx xxxx Green fuorescent protein (GFP) fusions are pervasively used to study structures and processes. Specifc GFP-binders are thus of great utility for detection, immobilization or manipulation of GFP-fused molecules. We determined structures of two designed ankyrin repeat proteins (DARPins), complexed with GFP, which revealed diferent but overlapping epitopes. Here we show a structure-guided design strategy that, by truncation and computational reengineering, led to a stable construct where both can bind simultaneously: by linkage of the two binders, fusion constructs were obtained that “wrap around” GFP, have very high afnities of about 10–30 pM, and extremely slow of-rates. They can be natively produced in E. coli in very large amounts, and show excellent biophysical properties. Their very high stability and afnity, facile site-directed functionalization at introduced unique lysines or cysteines facilitate many applications. As examples, we present them as tight yet reversible immobilization reagents for surface plasmon resonance, as fuorescently labelled monomeric detection reagents in fow cytometry, as pull-down ligands to selectively enrich GFP fusion proteins from cell extracts, and as afnity column ligands for inexpensive large-scale protein purifcation. We have thus described a general design strategy to create a “clamp” from two diferent high-afnity repeat proteins, even if their epitopes overlap. -
E2921.Full.Pdf
Noncatalytic aspartate at the exonuclease domain of PNAS PLUS proofreading DNA polymerases regulates both degradative and synthetic activities Alicia del Pradoa, Elsa Franco-Echevarríab, Beatriz Gonzálezb, Luis Blancoa, Margarita Salasa,1,2, and Miguel de Vegaa,1,2 aInstituto de Biología Molecular “Eladio Viñuela,” Consejo Superior de Investigaciones Cientificas (CSIC), Centro de Biología Molecular “Severo Ochoa,” (CSIC-Universidad Autónoma de Madrid), Cantoblanco, 28049 Madrid, Spain; and bDepartment of Crystallography and Structural Biology, Instituto de Química Física “Rocasolano,” (CSIC) 28006 Madrid, Spain Contributed by Margarita Salas, February 14, 2018 (sent for review October 30, 2017; reviewed by Charles C. Richardson and Eckard Wimmer) Most replicative DNA polymerases (DNAPs) are endowed with a 3′-5′ the 3′-end of the growing strand must be preferentially stabilized exonuclease activity to proofread the polymerization errors, gov- at the polymerization active site to allow multiple elongation cy- erned by four universally conserved aspartate residues belonging cles. Eventually, misinsertion of a 2′-deoxynucleoside-5′-mono- to the Exo I, Exo II, and Exo III motifs. These residues coordinate phosphate (dNMP) provokes a drastic drop of the elongation the two metal ions responsible for the hydrolysis of the last phos- catalytic rate, mainly due to the defective nucleolytic attack of the phodiester bond of the primer strand. Structural alignment of the mismatched 3′-end on the next incoming nucleotide. In addition, conserved exonuclease domain of DNAPs from families A, B, and C the terminal mispair provokes a disruption of contacts with minor has allowed us to identify an additional and invariant aspartate, groove hydrogen acceptors at the polymerization site, favoring the located between motifs Exo II and Exo III. -
Designing and Evaluating the MULTICOM Protein Local and Global
Cao et al. BMC Structural Biology 2014, 14:13 http://www.biomedcentral.com/1472-6807/14/13 RESEARCH ARTICLE Open Access Designing and evaluating the MULTICOM protein local and global model quality prediction methods in the CASP10 experiment Renzhi Cao1, Zheng Wang4 and Jianlin Cheng1,2,3* Abstract Background: Protein model quality assessment is an essential component of generating and using protein structural models. During the Tenth Critical Assessment of Techniques for Protein Structure Prediction (CASP10), we developed and tested four automated methods (MULTICOM-REFINE, MULTICOM-CLUSTER, MULTICOM-NOVEL, and MULTICOM- CONSTRUCT) that predicted both local and global quality of protein structural models. Results: MULTICOM-REFINE was a clustering approach that used the average pairwise structural similarity between models to measure the global quality and the average Euclidean distance between a model and several top ranked models to measure the local quality. MULTICOM-CLUSTER and MULTICOM-NOVEL were two new support vector machine-based methods of predicting both the local and global quality of a single protein model. MULTICOM- CONSTRUCT was a new weighted pairwise model comparison (clustering) method that used the weighted average similarity between models in a pool to measure the global model quality. Our experiments showed that the pairwise model assessment methods worked better when a large portion of models in the pool were of good quality, whereas single-model quality assessment methods performed better on some hard targets when only a small portion of models in the pool were of reasonable quality. Conclusions: Since digging out a few good models from a large pool of low-quality models is a major challenge in protein structure prediction, single model quality assessment methods appear to be poised to make important contributions to protein structure modeling. -
Some Studies on Protein Structure Alignment Algorithms
University of Windsor Scholarship at UWindsor Electronic Theses and Dissertations Theses, Dissertations, and Major Papers 2017 Some studies on protein structure alignment algorithms Shalini Bhattacharjee University of Windsor Follow this and additional works at: https://scholar.uwindsor.ca/etd Recommended Citation Bhattacharjee, Shalini, "Some studies on protein structure alignment algorithms" (2017). Electronic Theses and Dissertations. 7348. https://scholar.uwindsor.ca/etd/7348 This online database contains the full-text of PhD dissertations and Masters’ theses of University of Windsor students from 1954 forward. These documents are made available for personal study and research purposes only, in accordance with the Canadian Copyright Act and the Creative Commons license—CC BY-NC-ND (Attribution, Non-Commercial, No Derivative Works). Under this license, works must always be attributed to the copyright holder (original author), cannot be used for any commercial purposes, and may not be altered. Any other use would require the permission of the copyright holder. Students may inquire about withdrawing their dissertation and/or thesis from this database. For additional inquiries, please contact the repository administrator via email ([email protected]) or by telephone at 519-253-3000ext. 3208. Some studies on protein structure alignment algorithms By Shalini Bhattacharjee A Thesis Submitted to the Faculty of Graduate Studies through the School of Computer Science in Partial Fulfillment of the Requirements for the Degree of Master of Science at the University of Windsor Windsor, Ontario, Canada 2017 c 2017 Shalini Bhattacharjee Some studies on protein structure alignment algorithms by Shalini Bhattacharjee APPROVED BY: M. Hlynka Department of Mathematics and Statistics D. Wu School of Computer Science A. -
PROTEIN STRUCTURE PREDICTION Bioinformatic Approach Edited by IGOR F
www.fivephoton.com PROTEIN STRUCTURE PREDICTION Bioinformatic Approach edited by IGOR F. TSIGELNY Preface: Prediction of protein structure is very important today. Whereas more than 17,000 protein structures are stored in PDB, more than 110,000 proteins are stored only in SWISSPROT. The ratio of solved crystal structures to a number of discovered proteins to about 0.15, and I do not see any improvement of this value in the future. At the same time development of genomics has brought an overwhelming amount of DNA sequencing information, which can be and already is used for constructing the hypothetical proteins. This situation shows the great importance of protein structure prediction. The field is growing very rapidly. A simple analysis of publications shows that the number of articles having the words „protein structure prediction‟ has almost doubled since 1995. So many really great ideas are used as a basis for the current prediction systems. Some of them will evolve into the next generation of the prediction software but some of them, even very promising, will be lost and rediscovered in the future. Here we tried to include the variety of methods representing the most interesting concepts of current protein structure prediction. This compendium of ideas makes this book an invaluable source for scientists developing prediction methods. In many cases authors describe successful prediction methods and programs that make this book an invaluable source of information for numerous users of prediction software. The first chapter describes the protein structure prediction program PROSPECT that produces a globally optimal threading alignment for a typical threading energy function, and allows users to easily incorporate experimental data as constraints into the threading process. -
Structural Alignment Based Kernels for Protein Structure Classification
Structural Alignment based Kernels for Protein Structure Classification Sourangshu Bhattacharya [email protected] Chiranjib Bhattacharyya [email protected] Dept. of Computer Science and Automation, Indian Institute of Science, Bangalore - 560 012, India. Nagasuma Chandra [email protected] Bioinformatics Center, Indian Institute of Science, Bangalore - 560012, India. Abstract acid types. This view is taken by most structure align- Structural alignments are the most widely ment algorithms (Eidhammer et al., 2000), which are used tools for comparing proteins with low the most widely accepted methods for protein struc- sequence similarity. The main contribution ture comparison. of this paper is to derive various kernels on In this paper, we explore the idea of designing clas- proteins from structural alignments, which sifiers based on Support vector machines(SVMs) for do not use sequence information. Central proteins having low sequence similarity. More explic- to the kernels is a novel alignment algorithm itly our goal is to derive positive semi-definite ker- which matches substructures of fixed size us- nels motivated from structural alignments without us- ing spectral graph matching techniques. We ing sequence information. The hypothesis is that any derive positive semi-definite kernels which structure classification technique should capture the capture the notion of similarity between sub- notion of similarity defined by structural alignment structures. Using these as base more sophis- algorithms. Though there is lot of work on design- ticated kernels on protein structures are pro- ing kernels on protein sequences (Jaakkola et al., 1999; posed. To empirically evaluate the kernels we J.-P. Vert, 2004; Leslie & Kwang, 2004), to the best used a 40% sequence non-redundant struc- of our knowledge, there is relatively less work on ker- tures from 15 different SCOP superfamilies. -
Uncovering a Superfamily of Nickel-Dependent Hydroxyacid
www.nature.com/scientificreports OPEN Uncovering a superfamily of nickel‑dependent hydroxyacid racemases and epimerases Benoît Desguin 1*, Julian Urdiain‑Arraiza1, Matthieu Da Costa2, Matthias Fellner 3,4, Jian Hu4,5, Robert P. Hausinger 4,6, Tom Desmet 2, Pascal Hols 1 & Patrice Soumillion 1 Isomerization reactions are fundamental in biology. Lactate racemase, which isomerizes L‑ and D‑lactate, is composed of the LarA protein and a nickel‑containing cofactor, the nickel‑pincer nucleotide (NPN). In this study, we show that LarA is part of a superfamily containing many diferent enzymes. We overexpressed and purifed 13 lactate racemase homologs, incorporated the NPN cofactor, and assayed the isomerization of diferent substrates guided by gene context analysis. We discovered two malate racemases, one phenyllactate racemase, one α‑hydroxyglutarate racemase, two D‑gluconate 2‑epimerases, and one short‑chain aliphatic α‑hydroxyacid racemase among the tested enzymes. We solved the structure of a malate racemase apoprotein and used it, along with the previously described structures of lactate racemase holoprotein and D‑gluconate epimerase apoprotein, to identify key residues involved in substrate binding. This study demonstrates that the NPN cofactor is used by a diverse superfamily of α‑hydroxyacid racemases and epimerases, widely expanding the scope of NPN‑dependent enzymes. Chemical isomers exhibit subtle changes in their structures, yet can show dramatic diferences in biological properties1. Interconversions of isomers by isomerases are important in the metabolism of living organisms and have many applications in biocatalysis, biotechnology, and drug discovery2. Tese enzymes are divided into 6 classes, depending on the type of reaction catalyzed: racemases and epimerases, cis–trans isomerases, intramo- lecular oxidoreductases, intramolecular transferases, intramolecular lyases, and other isomerases3.