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methodology
analysis methods. The ProtaBank database, together with its analysis and visualization tools, will help scientists gain insights into sequencewactivity and structurewactivity relationships, improve our understanding of how proteins function, and ultimately facilitate the design of proteins with new and improved prop...
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web interface and API for data searching and analysis. The design and workflow for ProtaBank is summarized in Figure 1. Users can submit data into the database through the web interface; access to external databases such as PubMed,20 the PDB, and UniProt are provided to facilitate the entry of publication informatio...
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information. More advanced analysis and comparison tools are also available via the web Page 6 of 39 John Wiley & SonsProtein Science This article is protected by copyright. All rights reserved. 7interface. For example, users can do a sequence search with the Basic Local Alignment Search Tool (BLAST)21 and use visual...
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results), and the units associated with the numerical value (Fig. 2). ProtaBank also has separate corresponding tables to represent computational protocols and derived quantities, and to store qualitative data (e.g., folded/unfolded) or data expressed in terms of a range or limit (e.g., 20–30, >100). In addition to ...
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data on the protein that was engineered (i.e., the PDB file, if available), and experimental gene construct information. This information adds context and additional query and filter parameters to the PE data. Nonwpublished PE studies can also be input in a similar fashion. In these cases, the researchers and organi...
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Depositors of nonwpublished results may embargo the release of the data until publication. The ProtaBank schema design incorporates two crucial elements: (1) the full amino acid sequence of the protein is stored to facilitate comparison of mutants across different assays and studies, and (2) for each assay, informat...
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8we believe they are necessary to enable useful comparisons of results across different studies. Our reasoning is as follows. First, PE studies and databases13,16 typically describe a mutant by listing the changes to its protein sequence relative to a specified starting sequence. However, the starting sequences used...
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each mutant confounds comparisons, as any differences in the reported results could be due to differences in the background residues. ProtaBank addresses this issue by providing web forms and an API that parses the input mutant information to return the full sequence so it can be stored as such, allowing for a strai...
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techniques, which can greatly affect the results.22w24 The ProtaBank schema takes these issues into account. As outlined above, the database uses the assay_expassay table to describe the Page 8 of 39 John Wiley & SonsProtein Science This article is protected by copyright. All rights reserved. 9procedure that was used...
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relationships with a series of other tables (category, property, technique, units) that help categorize and describe the many ways these properties can be measured. The category table provides the general type of protein property that was engineered or studied (e.g., stability, activity, binding). The property table...
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ProtaBank are listed in Supporting Information, Table S1. Commonly used experimental or computational techniques are also provided to indicate how the property was assayed (e.g., circular dichroism, surface plasmon resonance). Note that the properties and techniques supplied are not comprehensive, and users can ente...
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details (e.g., authors, title, journal, date, abstract) can be fetched from PubMed, and the protein sequence can be retrieved from the PDB or UniProt. If available, structural data for the protein can be fetched from the PDB.
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was engineered or studied, the specific property measured, the technique employed, and the units used. All items except the assay name are specified by selecting from options in a dropwdown menu. Additional details can be included if desired. By entering this information, assays can be clearly defined and compared. ...
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for relevant studies queried by publication/study details (title, abstract, author), protein name, PDB ID, UniProt accession number, or protein sequence, (2) identify data and mutants related to a given protein sequence by BLAST search, (3) visualize mutational data mapped onto a threew dimensional (3D) protein struc...
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screenshot in which study analysis tools were used to visualize mutational data on a 3D protein structure. The visualizer is based on PV, an openwsource javascript protein viewer (https://biasmv.github.io/pv/index.html) that was extended to allow mutations to be represented Page 11 of 39 John Wiley & SonsProtein Scie...
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gradient, minimum, maximum, median, mean, proportion above a reference value, and median deviation from a reference value. In the study depicted here, Jacquier et al. investigated the effects of mutations on TEMw1 βwlactamase activity by computing the amoxicillin minimum inhibitory concentration (MIC) score for ~990...
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Utility and Discussion The following case studies demonstrate how ProtaBank search and analysis tools can aid in analyzing and interpreting PE data. Case study 1: Identify and compare data for a protein sequence Before beginning any PE study, a review of existing literature on the protein of interest provides
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a useful reference point. Therefore, a simple but important application of ProtaBank is to identify and compare previously measured properties of a given sequence. Because ProtaBank stores the full sequence information for each mutant, a simple query on a specified protein sequence retrieves all the relevant data fo...
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similar results when the temperature and pH were similar. These results suggest that the pH and/or temperature can have a notable effect on ∆Gu. Thus, in order to make meaningful comparisons of engineered mutants relative to the wild type, it is clearly important to select the
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assay parameters that can impact the results, and enable an informed evaluation of results obtained under different assay conditions. For theoretical and computational scientists, ProtaBank provides another valuable service—
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easy access to data sets that can be used to benchmark, test, and improve predictive methods. For example, the experimental results provided in this case study could be used to test theoretical Page 13 of 39 John Wiley & SonsProtein Science This article is protected by copyright. All rights reserved. 14methods aimed ...
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in the data reported for closely related sequences. By comparing results between a sequence and its mutants, the effects of mutation at a given position can be determined. The knowledge gained can then be used to guide the selection of positions and mutations in future engineering efforts. In this case study, we use...
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that are closely related to wildwtype G β1. Summary information is displayed in a mutant distribution heat map and a histogram showing the distribution of the number of mismatches (Fig. 4). The heat map [Fig. 4(A)] shows the number of sequences containing a mutation to a given amino acid at a given position; the wil...
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results In this case study, we use additional features of ProtaBank's "Identify and analyze sequence mutations" tool to perform further analyses on the closely related G β1 sequences retrieved in Case study 2 above. Plot one property vs. another For any two measured properties, users can plot one property vs. anot...
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Compare assay results A recently published study by Olson et al.38 used mRNA display and deep mutational scanning to determine the fitness of all single and double mutants of G β1. The authors further calculated a ∆∆G predictor (∆∆ Gscreen), which used their fitness values to predict the ∆ G change in protein stabi...
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comparing the predicted results to experimentally obtained ∆∆ Gs reported in the literature (∆∆Gliterature ). ProtaBank provides a feature that allows this type of comparison to be done quickly and easily. The “Compare assay to others by mutation” feature allows all the input mutants for one assay to be searched for...
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information. All the results can then be further sorted and filtered by background sequence, mutation, or study. We used this feature to reproduce the comparison of ∆∆ Gscreen to existing biochemical measurements of ∆∆ G as shown in the Olson et al. study.38 First, we did a "Compare assay to others by mutation" on t...
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these results to the set of 10 background sequences and single point mutants listed in the Olson et al. study [Fig. 6(B)]. Our filtered results match the data in their paper exactly except for one Page 16 of 39 John Wiley & SonsProtein Science This article is protected by copyright. All rights reserved. 17point—the m...
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This feature makes it easy to compare the results for the set of mutants in a given assay to those from any other group of assays (the properties measured can be the same or different). This allows one to see if new assay data is consistent with previously observed trends. It can also be used to identify protein pro...
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study, we look at experimental data from the Olson et al. Gβ1 study described above38 by mapping the effect of single mutations onto the crystal structure of the protein. By visualizing the data in this way, trends associated with structural features become more obvious than when viewed in a table or chart. In the ...
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view this data in 3D with the protein visualizer, which is accessible via the study analysis page. We could map the fitness data onto the G β1 backbone using the median deviation from the wildw type value color scheme to help identify residue positions that are sensitive to mutation, as we did for the βwlactamase stu...
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Further analysis and visualization capabilities are therefore provided. ProtaBank allows you to save the data values from the selected color scheme in the occupancy column of the PDB file so that other modeling or visualization software can be used. In this case study, we used visual molecular dynamics (VMD)43 softw...
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structural analysis thus helps explain why these residues are particularly sensitive to mutation and suggests that the observed sensitivity is likely due to disruption of the binding site rather than a destabilization of the G β1 fold.
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Concluding Remarks and Future Development ProtaBank offers an easily accessible cloudwbased modern database for PE data. It emphasizes the specification of detailed assay information and full protein sequences in an effort to ensure that all collected data is not just stored, but that data from diverse studies are c...
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19submissions directly from researchers, ProtaBank can incorporate the most recent results and be managed with fewer resources. Although this requires some effort on the part of the individual researcher, ProtaBank offers many benefits to submitters, including storing their data in an
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data, create plots and charts, and view results on the 3D structure. We have also started more advanced integration with protein structural data to allow for data selection and filtering on structural properties and to allow for computational predictions based on structural and sequence
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information. Future tools include incorporating computational methods to predict the effect of mutations on protein properties such as stability, binding, and activity. ProtaBank will provide a central location and valuable entry point for researchers to store, retrieve, compare, and analyze PE data. It will make it...
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results to guide their designs and provide valuable data sets that theoreticians can use as benchmarking cases in developing better predictive algorithms. We expect that ProtaBank will serve a pivotal role in centralizing PE data and leveraging the increasingly large amount of
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mutational data being generated. ProtaBank and its analysis tools will accelerate our ability to understand sequencewfunction relationships and greatly facilitate future protein design and engineering efforts. Page 19 of 39 John Wiley & SonsProtein Science This article is protected by copyright. All rights reserved. ...
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results obtained from a sequence search. Acknowledgments This work was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R44GM117961. The content is solely the responsibility of the authors and does not necessarily represent the official views of...
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References 1. Goodwin S, McPherson JD, McCombie WR (2016) Coming of age: ten years of nextw generation sequencing technologies. Nat Rev Genet 17:333w351. 2. Romero PA, Tran TM, Abate AR (2015) Dissecting enzyme function with microfluidicw based deep mutational scanning. Proc Natl Acad Sci USA 112:7159w7164. 3. Chen ...
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Cochran JR (2016) Highwthroughput analysis and protein engineering using microcapillary arrays. Nat Chem Biol 12:76w81. 4. Quan J, Saaem I, Tang N, Ma S, Negre N, Gong H, White KP, Tian J (2011) Parallel onw chip gene synthesis and application to optimization of protein expression. Nat Biotechnol 29:449w452. Page 20...
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Highwresolution mapping of protein sequencewfunction relationships. Nat Methods 7:741w 746. 6. Hietpas RT, Jensen JD, Bolon DNA (2011) Experimental illumination of a fitness landscape. Proc Natl Acad Sci USA 108:7896w7901. 7. Whitehead TA, Chevalier A, Song Y, Dreyfus C, Fleishman SJ, De Mattos C, Myers CA, Kamiset...
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Methods 11:801w807. 9. Wrenbeck EE, Faber MS, Whitehead TA (2017) Deep sequencing methods for protein engineering and design. Curr Opin Struct Biol 45:36w44. 10. Rose PW, Prlić A, Altunkaya A, Bi C, Bradley AR, Christie CH, Costanzo LD, Duarte JM, Dutta S, Feng Z, Green RK, Goodsell DS, Hudson B, Kalro T, Lowe R, P...
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21. Madden T. The BLAST Sequence Analysis Tool. In: Hoeppner M, Ostell J, Eds. (2013) The NCBI Handbook [Internet]. National Center for Biotechnology Information, Bethesda, MD, https://www.ncbi.nlm.nih.gov/books/NBK153387/ . Page 22 of 39 John Wiley & SonsProtein Science This article is protected by copyright. All ri...
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32. Choi EJ, Mayo SL (2006) Generation and analysis of proline mutants in protein G. Protein Eng Des Sel 19:285w289. 33. Davey JA, Damry AM, Goto NK, Chica RA (2017) Rational design of proteins that exchange on functional timescales. Nat Chem Biol 13:1280w1285. 34. Schaefer M, Sommer M, Karplus M (1997) pHwdependen...
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26Table I. Assay Details Help Explain Differences in ∆Gu Results for wild-type G β1 Study Reference ∆Gu (kcal/mol)a Techniqueb T (°C)c pH 57 Choi and Mayo, 200632 5.9d Thermal denaturation, circular dichroism 25 5.5 61 Gronenborn et al., 199629 5.6 GdmCl denaturation, fluorescence 25 5.4 72 Frank et al. , 199530 4....
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Figure 2. ProtaBank database schema showing the table for experimental data represented by a number (data_expfdatum, blue header) and all tables with foreign key relationships to it. Each table shows the field name (left) and the variable type for the field (right). Each datum in the data_expfdatum table has a forei...
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(study_study) that organizes the context in which the experiments were performed, an assay table (assay_expassay) that describes the procedure used to obtain the measurement, a sequence table (sequence_complex) that holds the protein sequence of the mutant, and a units table (data_unit) that describes the units of t...
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Figure 3. Screenshots of the web interface when using ProtaBank search and analysis tools. (A) A textwbased search for "ubiquitin" returns a sortable table containing all studies with ubiquitin in the protein name or study title. Clicking on the study ID at the left brings up the analysis page for
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that study. (B) The analysis page for a study on βwlactamase27 includes a protein visualizer in which mutational results are mapped onto the protein structure according to the selected color scheme. Here, Leu57 is highlighted in yellow and the single mutant data for that residue is Page 27 of 39 John Wiley & SonsProt...
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than (blue) the value of the reference at that position (white). Figure 4. Identifying and analyzing closely related mutants of G β1 in ProtaBank. (A) A BLAST search of the ProtaBank database finds ~1.3 million sequences that are closely related to wildw type G β1. The heat map shows the frequency of each residue at ...
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predictor values (∆∆ Gscreen) were plotted against experimental ∆∆ G values reported in the literature (∆∆ Gliterature ). (A) Unfiltered search of ProtaBank database identifies 343 mutant sequence pairs with both predicted and experimental ∆∆ G values. (B) Search filtered by the Page 28 of 39 John Wiley & SonsProtein...
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29mutations and background sequences from the Olson et al. study yields 82 pairs, reproducing their data. Note that ProtaBank identifies ~260 additional data points. Figure 7. Comparing fitness and proximity to the binding site for G β1 point mutants. The ProtaBank visualizer was used to map the Olson et al.38 fitne...
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red if more than 3.5 Å away. The structural analysis shows that most of the G β1 residues near the binding interface are particularly sensitive to mutation. Page 29 of 39 John Wiley & SonsProtein Science This article is protected by copyright. All rights reserved. Figure 1. ProtaBank design. Users can interact wit...
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Figure 2. ProtaBank database schema showing the table for experimental data represented by a number (data_expfdatum, blue header) and all tables with foreign key relationships to it. Each table shows the field name (left) and the variable type for the field (right). Each datum in the data_expfdatum table has a foreig...
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greater than (blue) the value of the reference at that position (white). 193x256mm (300 x 300 DPI) Page 32 of 39 John Wiley & SonsProtein Science This article is protected by copyright. All rights reserved. Figure 4. Identifying and analyzing closely related mutants of Gβ1 in ProtaBank. (A) A BLAST search of ...
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database identifies 343 mutant sequence pairs with both predicted and experimental ∆∆G values. (B) Search filtered by the mutations and background sequences from the Olson et al. study yields 82 pairs, reproducing their data. Note that ProtaBank identifies ~260 additional data points. 139x73mm (150 x 150 DPI) P...
verma-et-al-2024-investigation-of-rare-earth-element-binding-to-a-surface-bound-affinity-peptide-derived-from-ef-hand
introduction
■INTRODUCTION Rareearthelements (REEs)areessential inseveralemerging technologies suchaswindturbines, electricvehicles, computer memory, autocatalytic converters, magnetic resonance imaging, andsmartphones.1BecauseREEsarevaluableandhavelimited availability, therecovery oftheseelements fromindustrial waste streamsisanat...
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Thereisanurgentneedtoidentifyefficientseparation methods thatrecycleREEsfromwastestreamsandprovideasteady, domestic sourceoftheseelements. Varioustechniques have beenappliedtorecoverREEsfromthewastestreamssuchassolventextraction,3filtration,4ionexchange,5chemical precip- itation,6adsorption,7andelectrochemical processe...
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biobased approach withselective adsorption ofREEsrequires deepacquaintance withthesupportmaterials andtheligandof choicesuchaspeptides thatcanbegraftedonthedesiredsurface forselective separation ofREEs.Peptides aredesirable asthey areshortchainsofaminoacids(lessthan50)andarehighly tunableligandsthatareselective forions...
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Through isothermal titration calorimetry (ITC)experiments, theyfoundthatthethermodynamic properties ofioncomplex- ationstrongly varywithlanthanide ionsize,andmolecular dynamics (MD)simulations revealed thatthehighbinding affinityisachieved through complete iondehydration. In anotherinvestigation, Xuetal.16derivedapepti...
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(ITC)experiments wereperformed todetermine the thermodynamic parameters (KD,ΔH, ΔS,and ΔG)ofthe interaction between thepeptides andionsinsolutions. QCM-D wasconducted toshowthatsurface-bound peptides derived fromlanmodulin canbindREEsandtocharacterize thesurface- boundaffinityusingtheLangmuir adsorption modeltoestimate...
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particles wasdetermined inaproof-of-concept experiment. Overall,thisstudycharacterizes theproperties ofsurface-bound LanM1peptideforthefirsttimeanddemonstrates itspotential utilityinREEseparation forfurther optimization and exploration inthefuture. ■MATERIALS ANDMETHODS Materials. Thepeptidesequences inthisstudywereder...
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experiments wasprocured fromAirgas.Goldnanoparticles withsize lessthan100nm(powder), 99.9%trace,wereobtained fromSigma- Aldrich. PeptideDesign. Thepeptidesequences forbindingstudieswere designed fromEF-hand loopIoflanmodulin. Thesequence intended forREEbinding iscalledLanM1(Ac-CGGGDPDKDGTIDLKE-ACSAppliedMaterials &Inte...
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experiments, thesolutions weredegassed. Thefirstinjection pointwas removed duetothedilution/mixing effectandthebaseline was corrected priortofurtheranalysis. Thedataanalysiswasdonewith Origin7.0usingtheonesetofsite-fitting modeltocalculate thebindingconstant (Kd),enthalpy (ΔH),andentropy (ΔS).Adjustments to solutionpHw...
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experiments wereoperated inaflowmoduleat18°Candataflowrate of150 μL/min. Thefrequency decrease andincrease reflectmass accumulation andremovalonthesurface,respectively, anddissipation changesshowtheviscoelastic characteristics oftheadsorbed material. Afteracquiring astablebaseline withultrapure water,lanmodulin peptide...
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Adsorption Experiments onGoldNanoparticles (GNPs). A protocol wasprepared andusedtoestimate theadsorption ofREEson LanM1-functionalized GNPs.Inallexperiments, roughly8to12mgof GNPpowerwasaddedtoa2.0mLEppendorf tubeandtheexactweight ofGNPswascalculated bytakingtheweightofthetubebeforeandafter addingGNPs.Later,1mLofLanM1...
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usingthecolorimetric technique, theconcentration oftheREEwas estimated. Control experiments without GNPwereperformed to ensurethatnometalleachedfromthetubematerialintothesolution andnoREEabsorbed onthetubesurface.Apictorialrepresentation of thestep-by-step procedure usedforREEbindingongoldnanoparticles (GNPs) isshownin...
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between 5.0and5.5throughout theexperiment.■RESULTS ANDDISCUSSION Conformational Analysis andBinding SiteInvestiga- tion.Boththepeptides, LanM1andscrambled LanM1, are newlydesigned peptides, andaninitialbindinginvestigation was neededtoidentifytheirabilitytobindREEionsinsolution. Therefore, theabilitytobindtocerium(III)...
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usingcirculardichroism (CD)experiments, aswehavedone withotherEF-hand peptidesequences previously.16Severalexperiments wereperformed bykeepingthepeptideconcen- trationat100μMandvaryingthecerium(III) ionconcentration withintherangeof100to1000 μM.Theeffectofion concentration onthesecondary structure ofthepeptides was obs...
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additional control experiment conducted onpolyproline, whichdoesnotbindtocerium(III), showslittletonochange in1HNMRpeaksandchemical shiftsascerium(III) isadded (FigureS2). Ascerium(III) isaddedtoLanM1,weobservebroadening of peaksintherangesof0.75to1ppm,2.95to3.05,and3.75to 3.85ppm(gray-highlighted regionsinFigure4a,c,e...
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cerium(III), confirming CDandMDsimulation results.In contrast, scrambled LanM1hasthesamesidechainsasLanM1 butdoesnotbindcerium(III), indicating theimportance ofthe aminoacidsequence. Figure5.ITCrawdata,Wiseman plot,andone-sitebindingmodelfitfor(a)LanM1withcerium(III) ions,(b)scrambled LanM1withcerium(III) ions,(c)LanM1...
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Eu(III),andY(III))at303.15K.Inaddition, experiments on scrambled LanM1withcerium(III) ionswereconducted to serveasacomparison. Figure5a,bshowstheceriumtitration curves(rawdata),isotherm, andone-sitebindingmodelfitfor LanM1andscrambled LanM1,respectively. Thetitrationresults forneodymium andeuropium ionswithLanM1areprov...
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findings. Theresultsarealsoinagreement withWeiandco- workers23whofoundthatlanmodulin proteinimmobilized to magnetic nanoparticles (MNP-LanM) didnotadsorbnon- REEs. WealsotestedLanM1bindingaffinitywithcerium(III) at low-pH conditions. Thestudiesatlow-pH conditions are relevanttocoalminedrainages wherethedischarges areat...
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Binding Analysis ofImmobilized Peptides. Tounder- standthebindingaffinityoftheimmobilized peptidewithsome REEsandcompeting non-REEs, aquartzcrystalmicrobalance withdissipation (QCM-D) analysiswasperformed. Inatypical
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QCM-D experiment, ultrapure waterisintroduced onthegold sensortogenerate abaseline. Onceastablebaseline is established, peptide solution ofknownconcentration is introduced, andanegative shiftinfrequency isobserved, whichisproportional tothehydrated massloadingofthe peptideonthesurface.Rinsesareoftenemployed toremove we...
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peptides, control experiments wereconducted, whereno bindingwasobserved, asshowninFigureS8.Ourprevious studyshowsthatwhennopeptidewaspresentontheQCM sensor,noirreversible bindingwasobserved forphosphate,17 indicating thatallphosphate bindingseenisduetointeractions withpeptide−cerium films.Wealsoobserved thathigher LanM...
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respectively. Figure6displays experiments performed atthe lowestREEconcentrations wherebindingwasobserved, where thebluelinecorresponds tothefrequency shift,whilethered linecorresponds tothedissipation shift.Ultrapure waterserved asthebaseline fortheexperiment, whichwasimmediately followed bya6.0μMpeptidesolution. Anex...
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cerium(III).57Therefore, similarQCM-D experiments were performed withtwonon-REE Ca(II)andCu(II)competitor ions.Theresultsofthesurface-bound LanM1peptidewiththese ionsareprovided inFigureS11.Likethebulk,theLanM1 peptidedoesnotshowaffinityforeithercalciumorcopperions. Evenatahighercompetitor ionconcentration of29.0 μM,no...
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QCM-D experiments wereperformed atvariousREEion concentrations toestimate surface-bound LanM1dissociation constants forCe(III)andNd(III). Inacidminedrainage, the concentration ofCe(III)andNd(III)isthehighestamongother REEs,58whichmakesthispairaparticular interestforthat application. TheLangmuir adsorption isotherm mode...
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QCM-D experiments todescribe theadsorption process.59,60 Although, itisanidealmodelthatmaynotfullycapturethe complexity ofadsorption, itcanstillprovidevaluable insights intotheadsorption behavior. Themodelisgivenas q RC C Ke T e e d = + (2) whereqeisthephosphate loading(mol/cm2),RT(mol/cm2)is theLangmuir constant rela...
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experiment. Becauseofthehigherror,itisdifficulttodetermine ifthereisashiftforNd(III) uponpeptideimmobilization. However, theseresultsshowforthefirsttimethatsurface-bound LanM1peptides bindREEs,whichmotivates futurestudiesto explorehowimmobilization impactsthetrendsinKd.
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discussion
Selectivity Analysis ofImmobilized Peptides. Ina practical separation scheme,immobilized peptides areexposed toamixtureofREEs.Separation occursifthepeptidehasa higheraffinity(lowerKd)foroneREEoveranotherduetothe preferential partitioning oftheREEionontothesolidpeptide- containing phase.Fordilutesolutions, selectivity c...
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discussion
discussion hereinwillrefertogeneraltrendsandorderof magnitude differences, recognizing thecaveatthatthe lanmodulin proteindatainTable2represent amorechallenging separation ofneighbors Nd/PrthanNd/Ce�immobilized LanM1peptides exhibitselectivity thatisonparwiththeLanM proteinat0.5.Thisisinteresting becausetheKdoftheLanM ...
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experiments
Severalequilibrium adsorption experiments ofLanM1-GNPs atdifferent concentrations wereperformed forREEsCe(III), Nd(III), Eu(III), andY(III)andnon-REEs Ca(II)andthe estimated adsorption capacity fortheionsatdifferent concentrations isreported inTableS5.Acomparison ofaverage equilibrium adsorption capacities ofREEsandcom...
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experiments
experiment wasperformed using20mM2-(N-morpholino)- ethanesulfonic acid(MES)bufferatpH5.0with2.5mg/mL MNP-LanM and ∼62.93 μMTb(III),23whichhassome similarities toourexperiment inDIwateratpH5.0−5.5with 5−8mgGNP/mL and20−125 μMREE,servingasauseful comparison. Intheirstudy,theloadingonMNPswas2.67 ± 0.15 μmolLanMSpyCatcher/...
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TheresultsintheQCM-D experiment showaminimum dissipation duringpeptideloading,whichindicates arigidlayer formation andlowwatercontent; however, thedegreeof hydration ofthelayerisunknown. Nonetheless, themolar peptideloadingonGNPsisofsimilarorderofmagnitude tothat oftheSpyCatcher MNPs.Whenadsorbing inamonolayer, the mol...
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conclusion
■CONCLUSIONS Insummary, LanM1peptidederivedfromtheEF-hand loop1of lanmodulin wastestedforitsbindingaffinityfordifferent REEs, Ce(III),Nd(III), Eu(III),andY(III),bothinthebulkandwhen boundtoagoldsurface usingbothexperimental and computational techniques. TheabilityofCe(III)ionstobind withLanM1andscrambled LanM1wasconfir...
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andnuclearmagnetic resonance spectroscopy (NMR)analysis. Isothermal titration calorimetry (ITC)resultsshowedsponta- neousbindingofallREEstotheLanM1peptide.Thebinding wasenthalpically disfavored butwasdrivenbyapositivechange inentropy.Thedissociation constants fromITCwerecorrelated totheionicradiusofREEswithaKdof3.84±1....
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discussion
Quartzcrystalmicrobalance withdissipation (QCM-D) analysis wasperformed tocharacterize thebindingofREEsandnon- REEstosurface-immobilized LanM1. Thedissociation con- stantsobtained fromLangmuir modelfittingsuggested thatthe bindingaffinities forCe(III)andNd(III) withsurface-bound LanM1 wereestimated toberoughly ∼0.9and1...
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results
ITCresults,QCM-D results,Scatchard plot,Langmuir modelregression data,summary ofadsorption metrics usedintheselectivity analysis, estimated adsorption capacities forREEsusingGNPs,andderivation foratwo-
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discussion
stepScatchard analysis. Arepository oftheGROMCAS inputfilesiscreatedonGitHub: https://github.com/ gev28/Gromacs_input_file (PDF) ■AUTHOR INFORMATION Corresponding Author JulieRenner −Department ofChemicalandBiomolecular Engineering, CaseWesternReserveUniversity,Cleveland,Ohio 44106,UnitedStates; orcid.org/0000-0002-61...
verma-et-al-2024-investigation-of-rare-earth-element-binding-to-a-surface-bound-affinity-peptide-derived-from-ef-hand
acknowledgment
Theauthorsdeclarenocompeting financial interest.■ACKNOWLEDGMENTS TheauthorsthankMolecular Biotechnology CoreatCleveland ClinicandthankDr.Smarajit Bandyopadhyay, Director, Molecular Biotechnology Core,forhishelpwithCDandITC
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experiments
experiments. AspecialthankstoSayaniBiswas,agraduate student intheDepartment ofChemical andBiomolecular Engineering atOhioStateUniversity, forvalidating MD calculations. TheauthorsalsothankDr.JeffreyCapadona, aprofessor intheDepartment ofBiomedical Engineering atCase Western Reserve University, forallowing ustouseQCM-D ...
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references
Technology.■REFERENCES (1)Hossain, M.K.;Raihan,G.A.;Akbar,M.A.;Rubel,M.H.K.; Ahmed,M.H.;Khan,M.I.;Hossain, S.;Sen,S.K.;Jalal,M.I.E.;El- Denglawey, A.CurrentApplications andFuturePotential ofRareEarth OxidesinSustainable Nuclear, Radiation, andEnergyDevices: A Review.ACSAppl.Electron.Mater.2022,4(7),3327−3353. (2)Elbash...
verma-et-al-2024-investigation-of-rare-earth-element-binding-to-a-surface-bound-affinity-peptide-derived-from-ef-hand
methodology
Theaker, N.;Hsu-Kim, H.;Jiao,Y.Abiosorption-based approach for selective extraction ofrareearthelements fromcoalbyproducts. Sep. Purif.Technol.2020,241,No.116726. (8)Castrillejo, Y.;Bermejo, M.R.;Pardo,R.;Martínez, A.M.Useof electrochemical techniques forthestudyofsolubilization processes of cerium−oxide compounds andr...
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methodology
theextraction methods.J.Environ.Chem.Eng.2022,10(3), No.107704. (10)Chen,Z.;Li,Z.;Chen,J.;Kallem,P.;Banat,F.;Qiu,H.Recent advances inselective separation technologies ofrareearthelements: a review.J.Environ.Chem.Eng.2022,10(1),No.107104. (11)Bashiri,A.;Nikzad,A.;Maleki,R.;Asadnia, M.;Razmjou, A.Rare EarthElements Recov...
verma-et-al-2024-investigation-of-rare-earth-element-binding-to-a-surface-bound-affinity-peptide-derived-from-ef-hand
methodology
crystals: Anewmolecular dynamics method.J.Appl.Phys.1981,52 (12),7182−7190. (43)Cook,E.C.;Featherston, E.R.;Showalter, S.A.;Cotruvo, J.A. Structural BasisforRareEarthElement Recognition byMethylobacte- riumextorquens Lanmodulin. Biochemistry 2019,58(2),120−125. (44)Habenschuss, A.;Spedding, F.H.Thecoordination (hydrati...
verma-et-al-2024-investigation-of-rare-earth-element-binding-to-a-surface-bound-affinity-peptide-derived-from-ef-hand
experiments
(60)Azizian,S.;Eris,S.;Wilson,L.D.Re-evaluation ofthecentury- oldLangmuir isotherm formodeling adsorption phenomena in solution.Chem.Phys.2018,513,99−104. (61)Bertelsen, E.R.;Jackson,J.A.;Shafer,J.C.ASurveyofExtraction Chromatographic f-Element Separations Developed byE.P.Horwitz. SolventExtr.IonExch.2020,38(3),251−289...