Improving protein fold recognition and template-based modeling by employing probabilistic-based matching between predicted one-dimensional structural properties of query and corresponding native properties of templates

Yang, Yuedong; Faraggi, Eshel; Zhao, Huiying; Zhou, Yaoqi

doi:10.1093/bioinformatics/btr350

Cited by 304 publications

(252 citation statements)

References 49 publications

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“…We noted that unlike RNA, solvent accessible surface areas of amino acid residues in proteins have long been predicted with high accuracy (Zhou and Faraggi 2010), utilized in applications ranging from protein structure prediction (Karchin et al 2003;Yang et al 2011), functional site prediction (Wodak and Mendez 2004;Fischer et al 2008), and deleterious mutation classifications (Krishnan and Westhead 2003;Zhao et al 2013). Significant correlation of RNAsnap results to in vivo RNA accessibility indicates that the method will help in improving our qualitative and quantitative understanding of RNA structure and function in vivo beyond the secondary structural level for the first time.…”

Section: Discussionmentioning

confidence: 99%

Genome-scale characterization of RNA tertiary structures and their functional impact by RNA solvent accessibility prediction

Yang

Zhao

et al. 2016

RNA

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As most RNA structures are elusive to structure determination, obtaining solvent accessible surface areas (ASAs) of nucleotides in an RNA structure is an important first step to characterize potential functional sites and core structural regions. Here, we developed RNAsnap, the first machine-learning method trained on protein-bound RNA structures for solvent accessibility prediction. Built on sequence profiles from multiple sequence alignment (RNAsnap-prof), the method provided robust prediction in fivefold cross-validation and an independent test (Pearson correlation coefficients, r, between predicted and actual ASA values are 0.66 and 0.63, respectively). Application of the method to 6178 mRNAs revealed its positive correlation to mRNA accessibility by dimethyl sulphate (DMS) experimentally measured in vivo (r = 0.37) but not in vitro (r = 0.07), despite the lack of training on mRNAs and the fact that DMS accessibility is only an approximation to solvent accessibility. We further found strong association across coding and noncoding regions between predicted solvent accessibility of the mutation site of a single nucleotide variant (SNV) and the frequency of that variant in the population for 2.2 million SNVs obtained in the 1000 Genomes Project. Moreover, mapping solvent accessibility of RNAs to the human genome indicated that introns, 5 ′ cap of 5 ′ and 3 ′ cap of 3 ′ untranslated regions, are more solvent accessible, consistent with their respective functional roles. These results support conformational selections as the mechanism for the formation of RNA-protein complexes and highlight the utility of genome-scale characterization of RNA tertiary structures by RNAsnap. The server and its stand-alone downloadable version are available at http://sparks-lab.org.

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Section: Discussionmentioning

confidence: 99%

Genome-scale characterization of RNA tertiary structures and their functional impact by RNA solvent accessibility prediction

Yang

Zhao

et al. 2016

RNA

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“…Models were based on the template 3s57 chain a of the human aBH2 protein and were built and evaluated using the intFOLD, i-tassEr and ModFOLD4 servers and the sParKs-x and Modeler standalone programs. [73][74][75][76] Details of the modeling approach are provided in the Supplementary Material. the images of models were rendered using PyMOL.…”

Section: Expression and Tissue Distribution Of Dtet And Dnmt2mentioning

confidence: 99%

The mysterious presence of a 5-methylcytosine oxidase in theDrosophilagenome

et al. 2013

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“…As such, we adopted a protein threading approach, also called fold recognition, which uses the amino acid sequence to place each amino acid in the best-fit position based on other folds commonly found in nature. The initial structure created for tropoelastin by this method is fairly close to the expected general structure (34). Energy minimization was then performed on the folded structure, after which an MD simulation was performed at 300 K for 1,000 ps to equilibrate the system.…”

Section: Resultsmentioning

confidence: 99%

Ferroelectric switching of elastin

Liu

Cai

Zelisko

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Ferroelectricity has long been speculated to have important biological functions, although its very existence in biology has never been firmly established. Here, we present compelling evidence that elastin, the key ECM protein found in connective tissues, is ferroelectric, and we elucidate the molecular mechanism of its switching. Nanoscale piezoresponse force microscopy and macroscopic pyroelectric measurements both show that elastin retains ferroelectricity at 473 K, with polarization on the order of 1 μC/cm 2 , whereas coarse-grained molecular dynamics simulations predict similar polarization with a Curie temperature of 580 K, which is higher than most synthetic molecular ferroelectrics. The polarization of elastin is found to be intrinsic in tropoelastin at the monomer level, analogous to the unit cell level polarization in classical perovskite ferroelectrics, and it switches via thermally activated cooperative rotation of dipoles. Our study sheds light onto a long-standing question on ferroelectric switching in biology and establishes ferroelectricity as an important biophysical property of proteins. This is a critical first step toward resolving its physiological significance and pathological implications.F erroelectricity was first discovered in synthetic materials in 1920 when spontaneous polarization of Rochelle salt was found to be switchable by an external electric field (1). Ferroelectrics thus belongs to a larger class of pyroelectric materials that possess a unique polar axis, which, in turn, belongs to piezoelectrics exhibiting linear coupling between electric and mechanical fields (2). Because of these versatile properties, ferroelectric materials are promising for a wide range of technological applications in data storage, sensing, actuation, energy harvesting, and electro-optic devices (3). Biological tissues, such as bones and tendons, were first observed to be piezoelectric in 1950s (4), and shortly thereafter, pyroelectricity was discovered in a variety of biological materials as well (5, 6). Ever since then, ferroelectricity has been speculated for biological systems, and its potential physiological significance has been suggested (7). For example, it was hypothesized that the conformation transition in voltage-gated ion channels is ferroelectric in nature (8, 9). Nevertheless, indication of ferroelectricity in biological materials has only recently emerged from nanoscale piezoresponse force microscopy (PFM) studies (10-13).This work is motivated by our recent observation of PFM switching in elastin (12), which has generated quite a bit of excitement, although there is still considerable skepticism regarding the notion of biological ferroelectricity. Such reservation is understandable, given the unusual phenomenon of ferroelectric switching in biology, some ambiguities associated with PFM hysteresis, and a current lack of understanding of the basic science underpinning the switching mechanism. Indeed, there is neither macroscopic evidence of ferroelectric switching nor microscopic understan...

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Improving protein fold recognition and template-based modeling by employing probabilistic-based matching between predicted one-dimensional structural properties of query and corresponding native properties of templates

Abstract: The method is available as a SPARKS-X server at http://sparks.informatics.iupui.edu/

Cited by 304 publications

References 49 publications

Genome-scale characterization of RNA tertiary structures and their functional impact by RNA solvent accessibility prediction

Genome-scale characterization of RNA tertiary structures and their functional impact by RNA solvent accessibility prediction

The mysterious presence of a 5-methylcytosine oxidase in theDrosophilagenome

Ferroelectric switching of elastin

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