QRB DiscoveryPub Date : 2024-12-09eCollection Date: 2025-01-01DOI: 10.1017/qrd.2024.18
Finn Johnsson, Taner Karagöl, Alper Karagöl, Shuguang Zhang
{"title":"Structural bioinformatic study of six human olfactory receptors and their AlphaFold3 predicted water-soluble QTY variants and OR1A2 with an odorant octanoate and TAAR9 with spermidine.","authors":"Finn Johnsson, Taner Karagöl, Alper Karagöl, Shuguang Zhang","doi":"10.1017/qrd.2024.18","DOIUrl":"10.1017/qrd.2024.18","url":null,"abstract":"<p><p>The molecular mechanism of olfaction, namely, how we smell with limited olfactory receptors to recognize exceedingly diverse and large numbers of scents remains unknown despite the recent advances in chemistry, chemical, structural, and molecular biology. Olfactory receptors are notoriously difficult to study because they are fully embedded in the cell membrane. After decades of efforts and significant funding, there are only three olfactory receptor structures known. To understand olfaction, we carried out the structural bioinformatic study of six human olfactory receptors including OR51E1, OR51E2, OR52cs, OR1A1, OR1A2, TAAR9, and their AlphaFold3 predicted water-soluble QTY variants with odorants. We applied the QTY code to replace leucine (L) with glutamine (Q), isoleucine (I) and valine (V) with threonine (T), and phenylalanine (F) with tyrosine (Y) only in the transmembrane helices. Therefore, these QTY variants become water-soluble. We also present the superimposed structures of native olfactory receptors and their water-soluble QTY variants. The superimposed structures show remarkable similarity with RMSDs between 0.441 and 1.275 Å despite significant changes to the protein sequence of the transmembrane domains (43.03%-50.31%). We also show the differences in hydrophobicity surfaces between the native olfactory receptors and their QTY variants. Furthermore, we also used AlphaFold3 and molecular dynamics to study the odorant octanoate with OR1A2 and spermidine with TAAR9. Our bioinformatics studies provide insight into the differences between the hydrophobic helices and hydrophilic helices, and will likely further stimulate designs of water-soluble integral transmembrane proteins and other aggregated proteins.</p>","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"6 ","pages":"e2"},"PeriodicalIF":0.0,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
QRB DiscoveryPub Date : 2024-12-03eCollection Date: 2024-01-01DOI: 10.1017/qrd.2024.9
Kumar Naveen, Sandeep Bose, Chanbasha Basheer, Richard N Zare, Elumalai Gnanamani
{"title":"Handheld portable device for delivering capped silver nanoparticles for antimicrobial applications.","authors":"Kumar Naveen, Sandeep Bose, Chanbasha Basheer, Richard N Zare, Elumalai Gnanamani","doi":"10.1017/qrd.2024.9","DOIUrl":"10.1017/qrd.2024.9","url":null,"abstract":"<p><p>We describe a simple, cost-effective, green method for producing capped silver nanoparticles (Ag NPs) using a handheld portable mesh nebulizer. The precursor solution containing a 1:1 mixture of silver nitrate (AgNO<sub>3</sub>) and ligand (glycerol or sodium alginate) was sprayed using the nebulizer. The Ag NPs were generated in the water microdroplets within a few milliseconds under ambient conditions without any external reducing agent or action of a radiation source. The synthesized nanoparticles were characterized by using high-resolution transmission electron microscopy (HR-TEM), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction analysis (XRD), which validated the formation of Ag NPs. The synthesized glycerate-capped silver nanoparticles (Ag-gly NPs) were used as a catalyst to show the oxidative coupling of aniline to form azobenzene products with a yield of up to 61%. Experiments conducted using Ag NPs produced in the droplets demonstrated more than 99% antibacterial activity when contacting <i>Escherichia Coli.</i> Our in-situ synthesis-cum-fabrication technique using a portable sprayer represents a viable alternative to the existing fiber or hydrogel-based antimicrobial wound healing.</p>","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"5 ","pages":"e9"},"PeriodicalIF":0.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
QRB DiscoveryPub Date : 2024-12-03eCollection Date: 2024-01-01DOI: 10.1017/qrd.2024.11
Srijayee Ghosh, Sonja Schmid
{"title":"The potential of fluorogenicity for single molecule FRET and DyeCycling.","authors":"Srijayee Ghosh, Sonja Schmid","doi":"10.1017/qrd.2024.11","DOIUrl":"10.1017/qrd.2024.11","url":null,"abstract":"<p><p>Single Molecule Förster Resonance Energy Transfer (smFRET) is a popular technique to directly observe biomolecular dynamics in real time, offering unique mechanistic insight into proteins, ribozymes, and so forth. However, inevitable photobleaching of the fluorophores puts a stringent limit on the total time a surface-tethered molecule can be monitored, fundamentally limiting the information gain through conventional smFRET measurements. DyeCycling addresses this problem by using reversibly - instead of covalently - coupled FRET fluorophores, through which it can break the photobleaching limit and theoretically provide unlimited observation time. In this perspective paper, we discuss the potential of various fluorogenic strategies to suppress the background fluorescence caused by unbound, freely diffusing fluorophores inherent to the DyeCycling approach. In comparison to nanophotonic background suppression using zero-mode waveguides, the fluorogenic approach would enable DyeCycling experiments on regular glass slides with fluorogenic FRET probes that are quenched in solution and only fluoresce upon target binding. We review a number of fluorogenic approaches and conclude, among other things, that short-range quenching appears promising for realising fluorogenic DyeCycling on regular glass slides. We anticipate that our discussion will be relevant for all single-molecule fluorescence techniques that use reversible fluorophore binding.</p>","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"5 ","pages":"e8"},"PeriodicalIF":0.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
QRB DiscoveryPub Date : 2024-10-22eCollection Date: 2024-01-01DOI: 10.1017/qrd.2024.16
Giulia Palermo, Bengt Nordén
{"title":"The Future of Chemistry is through Computations.","authors":"Giulia Palermo, Bengt Nordén","doi":"10.1017/qrd.2024.16","DOIUrl":"10.1017/qrd.2024.16","url":null,"abstract":"","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"5 ","pages":"e7"},"PeriodicalIF":0.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
QRB DiscoveryPub Date : 2024-08-29eCollection Date: 2024-01-01DOI: 10.1017/qrd.2024.7
Yu Liu, Lei Cao, Yu Xia, Pan Pan, Lang Rao, Bolei Chen, Richard N Zare
{"title":"As air relative humidity increases, infectivity of SARS-CoV-2 decreases within water droplets.","authors":"Yu Liu, Lei Cao, Yu Xia, Pan Pan, Lang Rao, Bolei Chen, Richard N Zare","doi":"10.1017/qrd.2024.7","DOIUrl":"10.1017/qrd.2024.7","url":null,"abstract":"<p><p>Water droplets containing the SARS-CoV-2 virus, responsible for coronavirus 2019 transmission, were introduced into a controlled-temperature and -humidity chamber. The SARS-CoV-2 virus with green fluorescent protein tag in droplets was used to infect Caco-2 cells, with viability assessed through flow cytometry and microscopic counting. Whereas temperature fluctuations within typical indoor ranges (20°C-30°C) had minimal impact, we observed a notable decrease in infection rate as the surrounding air's relative humidity increased. By investigating humidity levels between 20% and 70%, we identified a threshold of ≥40% relative humidity as most effective in diminishing SARS-CoV-2 infectivity. We also found that damage of the viral proteins under high relative humidity may be responsible for the decrease in their activity. This outcome supports previous research demonstrating a rise in the concentration of reactive oxygen species within water droplets with elevated relative humidity.</p>","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"5 ","pages":"e6"},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
QRB DiscoveryPub Date : 2024-04-01DOI: 10.1017/qrd.2024.6
Robert Clark, Kahlan E. Newman, S. Khalid
{"title":"Titratable residues that drive RND efflux: insights from molecular simulations","authors":"Robert Clark, Kahlan E. Newman, S. Khalid","doi":"10.1017/qrd.2024.6","DOIUrl":"https://doi.org/10.1017/qrd.2024.6","url":null,"abstract":"","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"828 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140782010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
QRB DiscoveryPub Date : 2024-02-02DOI: 10.1017/qrd.2024.1
Shangze Xu, Lanyu Fan, Piotr Zaborniak, Ruidi Zhu, Haoyuan Ji, Katrina S Madden, J. V. de Souza, Agnieszka K. Bronowska
{"title":"“Druggability” of the PAS domains of human PASK kinase, a therapeutic target for metabolic and liver disorders","authors":"Shangze Xu, Lanyu Fan, Piotr Zaborniak, Ruidi Zhu, Haoyuan Ji, Katrina S Madden, J. V. de Souza, Agnieszka K. Bronowska","doi":"10.1017/qrd.2024.1","DOIUrl":"https://doi.org/10.1017/qrd.2024.1","url":null,"abstract":"","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"28 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139870955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
QRB DiscoveryPub Date : 2024-02-02DOI: 10.1017/qrd.2024.1
Shangze Xu, Lanyu Fan, Piotr Zaborniak, Ruidi Zhu, Haoyuan Ji, Katrina S Madden, J. V. de Souza, Agnieszka K. Bronowska
{"title":"“Druggability” of the PAS domains of human PASK kinase, a therapeutic target for metabolic and liver disorders","authors":"Shangze Xu, Lanyu Fan, Piotr Zaborniak, Ruidi Zhu, Haoyuan Ji, Katrina S Madden, J. V. de Souza, Agnieszka K. Bronowska","doi":"10.1017/qrd.2024.1","DOIUrl":"https://doi.org/10.1017/qrd.2024.1","url":null,"abstract":"","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"46 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139810852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
QRB DiscoveryPub Date : 2024-01-29DOI: 10.1017/qrd.2024.4
Ajith Harish
{"title":"Protein structures unravel the signatures and patterns of deep time evolution","authors":"Ajith Harish","doi":"10.1017/qrd.2024.4","DOIUrl":"https://doi.org/10.1017/qrd.2024.4","url":null,"abstract":"","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"231 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140489886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}