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Karlsson, Björn C. G.ORCID iD iconorcid.org/0000-0002-7392-0591
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Publications (10 of 63) Show all publications
Näsström, T., Andersson, P. O., Lejon, C. & Karlsson, B. C. G. (2019). Amyloid fibrils prepared using an acetylated and methyl amidated peptide model of the alpha-Synuclein NAC 71-82 amino acid stretch contain an additional cross-beta structure also found in prion proteins. Scientific Reports, 9, 1-14, Article ID 15949.
Open this publication in new window or tab >>Amyloid fibrils prepared using an acetylated and methyl amidated peptide model of the alpha-Synuclein NAC 71-82 amino acid stretch contain an additional cross-beta structure also found in prion proteins
2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, p. 1-14, article id 15949Article in journal (Refereed) Published
Abstract [en]

The 71-82 fragment of the non-amyloid-beta component (NAC) region of the Parkinson's disease (PD) and dementia with Lewy bodies (DLB) related protein alpha-Synuclein, has been reported to be important during protein misfolding. Although reports have demonstrated the importance of this fragment for the aggregation properties of the full-length protein, its exact role in pre-fibrillar oligomerisation, fibrillar growth and morphology has not yet been fully elucidated. Here, we provide evidence that fibrils prepared from an acetylated and methyl amidated peptide of the NAC 71-82 amino acid stretch of alpha-Synuclein are amyloid and contain, in addition to the cross-beta structure detected in the full-length protein fibrils, a cross-beta structure previously observed in prion proteins. These results shed light on the aggregation propensity of the NAC 71-82 amino acid stretch of the full-length protein but also the roles of the N- and C-terminal domains of alpha-Synuclein in balancing this aggregation propensity. The results also suggest that early aggregated forms of the capped NAC 71-82 peptide generated structures were stabilised by an anti-parallel and twisted beta-sheet motif. Due to its expected toxicity, this beta-sheet motif may be a promising molecular target for the development of therapeutic strategies for PD and DLB.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Biochemistry and Molecular Biology
Research subject
Chemistry, Biochemistry
Identifiers
urn:nbn:se:lnu:diva-90198 (URN)10.1038/s41598-019-52206-5 (DOI)000493898100057 ()31685848 (PubMedID)
Available from: 2019-11-21 Created: 2019-11-21 Last updated: 2019-11-21Bibliographically approved
Steinz, M. M., Persson, M., Aresh, B., Olsson, K., Cheng, A. J., Ahlstrand, E., . . . Lanner, J. T. (2019). Oxidative hotspots on actin promote skeletal muscle weakness in rheumatoid arthritis. JCI Insight, 4(9), 1-16, Article ID e126347.
Open this publication in new window or tab >>Oxidative hotspots on actin promote skeletal muscle weakness in rheumatoid arthritis
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2019 (English)In: JCI Insight, ISSN 2324-7703, Vol. 4, no 9, p. 1-16, article id e126347Article in journal (Refereed) Published
Abstract [en]

Skeletal muscle weakness in patients suffering from rheumatoid arthritis (RA) adds to their impaired working abilities and reduced quality of life. However, little molecular insight is available on muscle weakness associated with RA. Oxidative stress has been implicated in the disease pathogenesis of RA. Here we show that oxidative post-translational modifications of the contractile machinery targeted to actin result in impaired actin polymerization and reduced force production. Using mass spectrometry, we identified the actin residues targeted by oxidative 3-nitrotyrosine (3-NT) or malondialdehyde adduct (MDA) modifications in weakened skeletal muscle from mice with arthritis and patients afflicted by RA. The residues were primarily located to three distinct regions positioned at matching surface areas of the skeletal muscle actin molecule from arthritis mice and RA patients. Moreover, molecular dynamic simulations revealed that these areas, here coined “hotspots”, are important for the stability of the actin molecule and its capacity to generate filaments and interact with myosin. Together, these data demonstrate how oxidative modifications on actin promote muscle weakness in RA patients and provide novel leads for targeted therapeutic treatment to improve muscle function.

Place, publisher, year, edition, pages
American Society for Clinical Investigation, 2019
National Category
Physiology
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-82024 (URN)10.1172/jci.insight.126347 (DOI)000466814100015 ()2-s2.0-85070659458 (Scopus ID)
Available from: 2019-04-18 Created: 2019-04-18 Last updated: 2019-08-29Bibliographically approved
Nicholls, I. A., Olsson, G. D., Karlsson, B. C. G., Suriyanarayanan, S. & Wiklander, J. G. (2018). Theoretical and Computational Strategies in Molecularly Imprinted Polymer Development. In: Wlodzimierz Kutner, Piyush Sindhu Sharma (Ed.), Molecularly Imprinted Polymers for Analytical Chemistry Applications: (pp. 197-226). London: Royal Society of Chemistry
Open this publication in new window or tab >>Theoretical and Computational Strategies in Molecularly Imprinted Polymer Development
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2018 (English)In: Molecularly Imprinted Polymers for Analytical Chemistry Applications / [ed] Wlodzimierz Kutner, Piyush Sindhu Sharma, London: Royal Society of Chemistry, 2018, p. 197-226Chapter in book (Refereed)
Abstract [en]

Theoretical and computational studies of molecular imprinting have helped provide valuable insights concerning the nature of the molecular-level events underlying the recognition characteristics of molecularly imprinted materials. Here, we first present an overview of a thermodynamic treatment of factors governing the behaviour of these functional materials, and then a summary of the development and current status of the use of computational strategies for studying aspects of molecular imprinting and the resulting material properties.

Place, publisher, year, edition, pages
London: Royal Society of Chemistry, 2018
Series
Polymer Chemistry Series
National Category
Theoretical Chemistry
Research subject
Chemistry, Organic Chemistry
Identifiers
urn:nbn:se:lnu:diva-81879 (URN)10.1039/9781788010474-00197 (DOI)2-s2.0-85047140306 (Scopus ID)978-1-78262-647-3 (ISBN)978-1-78801-047-4 (ISBN)978-1-78801-427-4 (ISBN)
Available from: 2019-04-12 Created: 2019-04-12 Last updated: 2019-08-29Bibliographically approved
Karlsson, B. C. G. & Friedman, R. (2017). Dilution of whisky - the molecular perspective. Scientific Reports, 7(6489)
Open this publication in new window or tab >>Dilution of whisky - the molecular perspective
2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, no 6489Article in journal (Refereed) Published
Abstract [en]

Whisky is distilled to around 70% alcohol by volume (vol-%) then diluted to about 40 vol-%, and often drunk after further slight dilution to enhance its taste. The taste of whisky is primarily associated with amphipathic molecules, such as guaiacol, but why and how dilution enhances the taste is not well understood. We carried out computer simulations of water-ethanol mixtures in the presence of guaiacol, providing atomistic details on the structure of the liquid mixture. We found that guaiacol is preferentially associated with ethanol, and, therefore, primarily found at the liquid-air interface in mixtures that contain up to 45 vol-% of ethanol. At ethanol concentrations of 59 vol-% or higher, guaiacol is increasingly surrounded by ethanol molecules and is driven to the bulk. This indicates that the taste of guaiacol in the whisky would be enhanced upon dilution prior to bottling. Our findings may apply to other flavour-giving amphipathic molecules and could contribute to optimising the production of spirits for desired tastes. Furthermore, it sheds light on the molecular structure of water-alcohol mixtures that contain small solutes, and reveals that interactions with the water may be negligible already at 89 vol-% of ethanol.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017
Keywords
Whisky, dilution, guaiacol
National Category
Physical Chemistry Theoretical Chemistry
Research subject
Chemistry, Biochemistry; Chemistry, Organic Chemistry; Chemistry, Physical Chemistry
Identifiers
urn:nbn:se:lnu:diva-67349 (URN)10.1038/s41598-017-06423-5 (DOI)000407863100001 ()2-s2.0-85027838994 (Scopus ID)
Funder
Swedish National Infrastructure for Computing (SNIC), SNIC/2014-1-404 SNIC/2015-1-444
Note

Correction published in: Scientific Reports, 2018, vol 8, Article number 16448. DOI: 10.1038/s41598-018-34169-1

Available from: 2017-08-22 Created: 2017-08-22 Last updated: 2019-08-29Bibliographically approved
Shoravi, S., Olsson, G. D., Karlsson, B. C. G., Bexborn, F., Abghoui, Y., Hussain, J., . . . Nicholls, I. A. (2016). In silico screening of molecular imprinting prepolymerization systems: oseltamivir selective polymers through full-system molecular dynamics-based studies. Organic and biomolecular chemistry, 14(18), 4210-4219
Open this publication in new window or tab >>In silico screening of molecular imprinting prepolymerization systems: oseltamivir selective polymers through full-system molecular dynamics-based studies
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2016 (English)In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 14, no 18, p. 4210-4219Article in journal (Refereed) Published
Abstract [en]

All-component molecular dynamics studies were used to probe a library of oseltamivir molecularly imprinted polymer prepolymerization mixtures. Polymers included one of five functional monomers (acrylamide, hydroxyethylmethacrylate, methacrylic acid, 2-(triflouromethyl)acrylic acid, 4-vinylpyridine) and one of three porogens (acetonitrile, chloroform, methanol) combined with the crosslinking agent ethylene glycol dimethacrylate and initiator 2,2'-azobis(2-methylpropionitrile). Polymers were characterized by nitrogen gas sorption measurements and SEM, and affinity studies performed using radioligand binding in various media. In agreement with the predictions made from the simulations, polymers prepared in acetonitrile using either methacrylic or trifluoromethacrylic acid demonstrated the highest affinities for oseltamivir. Further, the ensemble of interactions observed in the methanol system provided an explanation for the morphology of polymers prepared in this solvent. The materials developed here offer potential for use in solid-phase extraction or for catalysis. The results illustrate the strength of this in silico strategy as a potential prognostic tool in molecularly imprinted polymer design.

National Category
Organic Chemistry
Research subject
Chemistry, Organic Chemistry
Identifiers
urn:nbn:se:lnu:diva-53319 (URN)10.1039/c6ob00305b (DOI)000375610600007 ()2-s2.0-84967333692 (Scopus ID)
Available from: 2016-06-10 Created: 2016-06-10 Last updated: 2018-11-02Bibliographically approved
Samyn, D. R., Van der Veken, J., Van Zeebroeck, G., Persson, B. L. & Karlsson, B. C. G. (2016). Key Residues and Phosphate Release Routes in the Saccharomyces cerevisae Pho84 Transceptor - The Role of Tyr179 in Functional Regulation. Journal of Biological Chemistry, 291(51), 26388-26398
Open this publication in new window or tab >>Key Residues and Phosphate Release Routes in the Saccharomyces cerevisae Pho84 Transceptor - The Role of Tyr179 in Functional Regulation
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2016 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 291, no 51, p. 26388-26398Article in journal (Refereed) Published
Abstract [en]

Pho84, a major facilitator superfamily (MFS) protein, is the main high-affinity Pi transceptor in Saccharomyces cerevisiae. Although transport mechanisms have been suggested for other MFS members, the key residues and molecular events driving transport by Pi: H+ symporters are unclear. The current Pho84 transport model is based on the inward-facing occluded crystal structure of the Pho84 homologue PiPT in the fungus Piriformospora indica. However, this model is limited by the lack of experimental data on the regulatory residues for each stage of the transport cycle. In this study, an open, inward-facing conformation of Pho84 was used to study the release of Pi. A comparison of this conformation with the model for Pi release in PiPT revealed that Tyr(179) in Pho84 (Tyr150 in PiPT) is not part of the Pi binding site. This difference may be due to a lack of detailed information on the Pi release step in PiPT. Molecular dynamics simulations of Pho84 in which a residue adjacent to Tyr(179), Asp(178), is protonated revealed a conformational change in Pho84 from an open, inward-facing state to an occluded state. Tyr(179) then became part of the binding site as was observed in the PiPT crystal structure. The importance of Tyr(179) in regulating Pi release was supported by site-directed mutagenesis and transport assays. Using trehalase activity measurements, we demonstrated that the release of Pi is a critical step for transceptor signaling. Our results add to previous studies on PiPT, creating a more complete picture of the proton-coupled Pi transport cycle of a transceptor.

Keywords
Pho84, Saccharomyces cerevisiae, Molecular dynamics, membrane protein, transport
National Category
Biochemistry and Molecular Biology Biophysics
Research subject
Chemistry, Biochemistry
Identifiers
urn:nbn:se:lnu:diva-60171 (URN)10.1074/jbc.M116.738112 (DOI)000391568200013 ()2-s2.0-85006241160 (Scopus ID)
Funder
The Crafoord Foundation, 20150874Swedish National Infrastructure for Computing (SNIC), SNIC 2014/1-404 SNIC 2015/1-444
Available from: 2017-01-24 Created: 2017-01-24 Last updated: 2018-11-02Bibliographically approved
Golker, K., Karlsson, B. C. G., Wiklander, J. G., Rosengren, A. M. & Nicholls, I. A. (2015). Hydrogen bond diversity in the pre-polymerization stage contributes to morphology and MIP-template recognition–MAA versus MMA. European Polymer Journal, 66, 558-568
Open this publication in new window or tab >>Hydrogen bond diversity in the pre-polymerization stage contributes to morphology and MIP-template recognition–MAA versus MMA
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2015 (English)In: European Polymer Journal, ISSN 0014-3057, E-ISSN 1873-1945, Vol. 66, p. 558-568Article in journal (Refereed) Published
Abstract [en]

This report demonstrates that the diversity of hydrogen bond interactions present in molecularly imprinted polymer pre-polymerization mixtures, typically associated with binding-site heterogeneity, can also contribute to morphological characteristics that may influence polymer–template recognition. Comparisons have been made between a series of bupivacaine molecularly imprinted methacrylic acid (MAA)–ethylene glycol dimethacrylate (EGDMA) copolymers and a series of analogous methyl methacrylate (MMA)–EGDMA copolymers using comprehensive molecular dynamics studies of the respective pre-polymerization mixtures, template–polymer binding studies and detailed BET surface area and BJH porosity analyses. The role of the carboxylic acid functionality of MAA, and in particular the acidic proton, in generating morphological features conducive to analyte access (slit-like rather than ink bottle-like structures) and recognition is discussed.

Place, publisher, year, edition, pages
Pergamon Press, 2015
National Category
Materials Chemistry
Research subject
Chemistry, Organic Chemistry
Identifiers
urn:nbn:se:lnu:diva-42601 (URN)10.1016/j.eurpolymj.2015.03.018 (DOI)000353854000057 ()2-s2.0-84928389138 (Scopus ID)
Available from: 2015-04-15 Created: 2015-04-15 Last updated: 2018-11-02Bibliographically approved
Olsson, G. D., Niedergall, K., Bach, M., Karlsson, B. C. G., Tovar, G. & Nicholls, I. A. (2015). Simulation of imprinted emulsion prepolymerization mixtures. Polymer journal, 47(12), 827-830
Open this publication in new window or tab >>Simulation of imprinted emulsion prepolymerization mixtures
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2015 (English)In: Polymer journal, ISSN 0032-3896, E-ISSN 1349-0540, Vol. 47, no 12, p. 827-830Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to develop protocols for and evaluate the use of all-atom full system molecular dynamic (MD) simulations of emulsion systems in the development of molecularly imprinted polymers (MIPs). Here, we report on the first, to the best of our knowledge, use of all-component MD studies to simulate and evaluate MIP miniemulsion prepolymerization mixtures; in this case, the mixtures used in the synthesis of a series of MIP-nanoparticles (MIP-NPs).

National Category
Organic Chemistry
Research subject
Chemistry, Organic Chemistry
Identifiers
urn:nbn:se:lnu:diva-48813 (URN)10.1038/pj.2015.63 (DOI)000366047900008 ()2-s2.0-84949442668 (Scopus ID)
Available from: 2016-01-19 Created: 2016-01-15 Last updated: 2018-11-02Bibliographically approved
Nicholls, I. A., Chavan, S., Golker, K., Karlsson, B. C. G., Olsson, G. D., Rosengren, A. M., . . . Wiklander, J. G. (2015). Theoretical and Computational Strategies for the Study of the Molecular Imprinting Process and Polymer Performance. In: Mattiasson, B. & Ye, L. (Ed.), Molecularly Imprinted Polymers in Biotechnology: (pp. 25-50). Berlin: Springer
Open this publication in new window or tab >>Theoretical and Computational Strategies for the Study of the Molecular Imprinting Process and Polymer Performance
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2015 (English)In: Molecularly Imprinted Polymers in Biotechnology / [ed] Mattiasson, B. & Ye, L., Berlin: Springer, 2015, p. 25-50Chapter in book (Refereed)
Abstract [en]

The development of in silico strategies for the study of the molecular imprinting process and the properties of molecularly imprinted materials has been driven by a growing awareness of the inherent complexity of these systems and even by an increased awareness of the potential of these materials for use in a range of application areas. Here we highlight the development of theoretical and computational strategies that are contributing to an improved understanding of the mechanisms underlying molecularly imprinted material synthesis and performance, and even their rational design.

Place, publisher, year, edition, pages
Berlin: Springer, 2015
Series
Advances in Biochemical Engineering-Biotechnology, ISSN 0724-6145 ; 150
National Category
Polymer Technologies
Research subject
Chemistry, Organic Chemistry
Identifiers
urn:nbn:se:lnu:diva-42600 (URN)10.1007/10_2015_318 (DOI)000365222300003 ()2-s2.0-84938411248 (Scopus ID)978-3-319-20729-2 (ISBN)978-3-319-20728-5 (ISBN)
Available from: 2015-04-15 Created: 2015-04-15 Last updated: 2018-11-02Bibliographically approved
Golker, K., Karlsson, B. C. G., Rosengren, A. M. & Nicholls, I. A. (2014). A Functional Monomer Is Not Enough: Principal Component Analysis of the Influence of Template Complexation in Pre-Polymerization Mixtures on Imprinted Polymer Recognition and Morphology. International Journal of Molecular Sciences, 15(11), 20572-20584
Open this publication in new window or tab >>A Functional Monomer Is Not Enough: Principal Component Analysis of the Influence of Template Complexation in Pre-Polymerization Mixtures on Imprinted Polymer Recognition and Morphology
2014 (English)In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 15, no 11, p. 20572-20584Article in journal (Refereed) Published
Abstract [en]

In this report, principal component analysis (PCA) has been used to explore the influence of template complexation in the pre-polymerization phase on template molecularly imprinted polymer (MIP) recognition and polymer morphology. A series of 16 bupivacaine MIPs were studied. The ethylene glycol dimethacrylate (EGDMA)-crosslinked polymers had either methacrylic acid (MAA) or methyl methacrylate (MMA) as the functional monomer, and the stoichiometry between template, functional monomer and crosslinker was varied. The polymers were characterized using radioligand equilibrium binding experiments, gas sorption measurements, swelling studies and data extracted from molecular dynamics (MD) simulations of all-component pre-polymerization mixtures. The molar fraction of the functional monomer in the MAA-polymers contributed to describing both the binding, surface area and pore volume. Interestingly, weak positive correlations between the swelling behavior and the rebinding characteristics of the MAA-MIPs were exposed. Polymers prepared with MMA as a functional monomer and a polymer prepared with only EGDMA were found to share the same characteristics, such as poor rebinding capacities, as well as similar surface area and pore volume, independent of the molar fraction MMA used in synthesis. The use of PCA for interpreting relationships between MD-derived descriptions of events in the pre-polymerization mixture, recognition properties and morphologies of the corresponding polymers illustrates the potential of PCA as a tool for better understanding these complex materials and for their rational design.

Keywords
molecularly imprinted polymer, molecular dynamics, molecular recognition, molecular imprinting, principal component analysis, chemometrics
National Category
Organic Chemistry
Research subject
Chemistry, Organic Chemistry
Identifiers
urn:nbn:se:lnu:diva-39134 (URN)10.3390/ijms151120572 (DOI)000345529200072 ()2-s2.0-84910128229 (Scopus ID)
Available from: 2015-01-15 Created: 2015-01-15 Last updated: 2018-11-02Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-7392-0591

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