CHEM Faculty Publications

Permanent URI for this collection


Recent Submissions

Now showing 1 - 5 of 506
  • Item
    Multiplatform High-Definition Ion Mobility Separations of the Largest Epimeric Peptides
    (American Chemical Society, 2024-02) Thurman, Hayden A.; Wijegunawardena, Gayani; Berthias, Francis; Williamson, David L.; Wu, Haifan; Nagy, Gabe; Jensen, Ole N.; Shvartsburg, Alexandre A.
    Ion mobility spectrometry (IMS) coupled to mass spectrometry (MS) has become a versatile tool to fractionate complex mixtures, distinguish structural isomers, and elucidate molecular geometries. Along with the whole MS field, IMS/MS advances to ever larger species. A topical proteomic problem is the discovery and characterization of d-amino acid-containing peptides (DAACPs) that are critical to neurotransmission and toxicology. Both linear IMS and FAIMS previously disentangled D/L epimers with up to ~30 residues. In the first study using all three most powerful IMS methodologies--trapped IMS, cyclic IMS, and FAIMS--we demonstrate baseline resolution of the largest known D/L peptides (CHH from $Homarus americanus$ with 72 residues) with a dynamic range up to 100. This expands FAIMS analyses of isomeric modified peptides, especially using hydrogen-rich buffers, to the ~50-100 residue range of small proteins. The spectra for D and L are unprecedentedly strikingly similar except for a uniform shift of the separation parameter, indicating the conserved epimer-specific structural elements across multiple charge states and conformers. As the interepimer resolution tracks the average for smaller DAACPs, the IMS approaches could help search for yet larger DAACPs. The a priori method to calibrate cyclic (including multipass) IMS developed here may be broadly useful.
  • Item
    SumoPred-PLM: human SUMOylation and SUMO2/3 sites Prediction using Pre-trained Protein Language Model
    (Oxford University Press, 2024-03) Palacios, Andrew Vargas; Acharya, Pujan; Peidl, Anthony Stephen; Beck, Moriah R.; Blanco, Eduardo; Mishra, Avdesh; Bawa-Khalfe, Tasneem; Pakhrin, Subash C.
    SUMOylation is an essential post-translational modification system with the ability to regulate nearly all aspects of cellular physiology. Three major paralogues SUMO1, SUMO2 and SUMO3 form a covalent bond between the small ubiquitin-like modifier with lysine residues at consensus sites in protein substrates. Biochemical studies continue to identify unique biological functions for protein targets conjugated to SUMO1 versus the highly homologous SUMO2 and SUMO3 paralogues. Yet, the field has failed to harness contemporary AI approaches including pre-trained protein language models to fully expand and/or recognize the SUMOylated proteome. Herein, we present a novel, deep learning-based approach called SumoPred-PLM for human SUMOylation prediction with sensitivity, specificity, Matthew's correlation coefficient, and accuracy of 74.64%, 73.36%, 0.48% and 74.00%, respectively, on the CPLM 4.0 independent test dataset. In addition, this novel platform uses contextualized embeddings obtained from a pre-trained protein language model, ProtT5-XL-UniRef50 to identify SUMO2/3-specific conjugation sites. The results demonstrate that SumoPred-PLM is a powerful and unique computational tool to predict SUMOylation sites in proteins and accelerate discovery.
  • Item
    Understanding and Tuning Magnetism in Layered Ising-Type Antiferromagnet FePSe$_3$ for Potential 2D Magnet
    (John Wiley and Sons Inc, 2024-01) Basnet, Rabindra; Patel, Taksh; Wang, Jian; Upreti, Dinesh; Chhetri, Santosh K.; Acharya, Gokul; Nabi, Md Rafique Un; Sakon, Josh; Hu, Jin
    Recent developments in 2D magnetic materials have motivated the search for new van der Waals magnetic materials, especially Ising-type magnets with strong magnetic anisotropy. Fe-based MPX$_3$ ($M$ = transition metal, $X$ = chalcogen) compounds such as FePS$_3$ and FePSe$_3$ both exhibit an Ising-type magnetic order, but FePSe$_3$ receives much less attention compared to FePS$_3$. This work focuses on establishing the strategy to engineer magnetic anisotropy and exchange interactions in this less-explored compound. Through chalcogen and metal substitutions, the magnetic anisotropy is found to be immune against S substitution for Se whereas tunable only with heavy Mn substitution for Fe. In particular, Mn substitution leads to a continuous rotation of magnetic moments from the out-of-plane direction toward the in-plane. Furthermore, the magnetic ordering temperature displays non-monotonic doping dependence for both chalcogen and metal substitutions but due to different mechanisms. These findings provide deeper insight into the Ising-type magnetism in this important van der Waals material, shedding light on the study of other Ising-type magnetic systems as well as discovering novel 2D magnets for potential applications in spintronics.
  • Item
    Synthesis, crystal and electronic structures, linear and nonlinear optical properties, and photocurrent response of oxyhalides CeHaVIO$_4$ (Ha = Cl, Br; VI = Mo, W)
    (Royal Society of Chemistry, 2023-12) Jiao, Zixian; Quah, Jasmine; Syed, Tajamul Hussain; Wei, Wei; Zhang, Bingbing; Wang, Fei; Wang, Jian
    Four heteroanionic oxyhalides, CeClMoO$_4$, CeBrMoO$_4$, CeClWO$_4$, and CeBrWO$_4$, have been studied as multifunctional materials, which show a combination of good second harmonic generation (SHG) response and photocurrent signals. Millimeter-sized CeHaVIO$_4$ (Ha = Cl, Br; VI = Mo, W) crystals were grown by halide salt flux. The crystal structure of CeHaVIO$_4$ crystals was accurately determined by single-crystal X-ray diffraction. CeClMoO$_4$, CeBrMoO$_4$, and CeBrWO$_4$ are isostructural to each other, and crystallize in the acentric LaBrMoO4 structure type. CeClWO$_4$ crystallizes in a new structure type with unit cell parameters of $a$ = 19.6059(2) Å, $b$ = 5.89450(10) Å, $c$ = 7.80090(10) Å, and β = 101.4746(8)°. The bandgaps of CeHaVIO$_4$ fall into the range of 2.8(1)-3.1(1) eV, which are much smaller than those of isotypic LaHaVIO$_4$ (Ha = Cl, Br; VI = Mo, W) in the range of 3.9(1)-4.3(1) eV. The narrowing of bandgaps in CeHaVIO$_4$ originates from the presence of partially filled 4f orbitals of cerium atoms, which was confirmed by density functional theory (DFT) calculations. The moderate bandgaps make CeHaVIO$_4$ suitable for infrared nonlinear optical (IR NLO) applications. CeBrMoO$_4$ and CeBrWO$_4$ exhibit moderate SHG responses of 0.58x AGS and 0.46x AGS, respectively, and are both type-I phase-matching materials. Moderate SHG response, easy growth of crystals, high ambient stability, and type-I phase-matching behavior make CeBrMoO$_4$ and CeBrWO$_4$ great materials for IR NLO applications. CeHaVIO$_4$ films also exhibited good photocurrent response upon light radiation. This work demonstrates the rich structural chemistry of the REHaVIO$_4$ (RE = Y, La-Lu; Ha = Cl, Br; VI = Mo, W) family and the potential presence of more multifunctional materials.
  • Item
    A chaperone-like function of FUS ensures TAZ condensate dynamics and transcriptional activation
    (Nature Research, 2024-01) Shao, Yangqing; Shu, Xin; Lu, Yi; Zhu, Wenxuan; Li, Ran; Fu, Huanyi; Li, Chengyu; Sun, Wei; Li, Zhuo; Zhang, Yitong; Cao, Xiaolei; Ye, Xifu; Ajiboye, Emmanuel; Zhao, Bin; Zhang, Long; Wu, Haifan; Feng, Xin-Hua; Yang, Bing; Lu, Huasong
    The Hippo pathway has important roles in organ development, tissue homeostasis and tumour growth. Its downstream effector TAZ is a transcriptional coactivator that promotes target gene expression through the formation of biomolecular condensates. However, the mechanisms that regulate the biophysical properties of TAZ condensates to enable Hippo signalling are not well understood. Here using chemical crosslinking combined with an unbiased proteomics approach, we show that FUS associates with TAZ condensates and exerts a chaperone-like effect to maintain their proper liquidity and robust transcriptional activity. Mechanistically, the low complexity sequence domain of FUS targets the coiled-coil domain of TAZ in a phosphorylation-regulated manner, which ensures the liquidity and dynamicity of TAZ condensates. In cells lacking FUS, TAZ condensates transition into gel-like or solid-like assembles with immobilized TAZ, which leads to reduced expression of target genes and inhibition of pro-tumorigenic activity. Thus, our findings identify a chaperone-like function of FUS in Hippo regulation and demonstrate that appropriate biophysical properties of transcriptional condensates are essential for gene activation.