Browsing by Author "Veliparambil Subrahmanian, Manu"

Now showing 1 - 9 of 9
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    Data for AI-designed NMR spectroscopy RF pulses for fast acquisition at high and ultra-high magnetic fields
    (2023-06-15) Veliparambil Subrahmanian, Manu; Veglia, Gianluigi; vegli001@umn.edu; Veglia, Gianluigi; Veglia Lab
    The data contains RF shapes for NMR spectroscopy designed using an evolutionary algorithm and artificial intelligence. These new RF pulses cover significantly broader bandwidths for 1H and 15N nuclei and allow rapid spectra acquisition. We also re-engineered the basic transverse relaxation optimized spectroscopy experiment (RAPID-TROSY) which can enhance the spectral sensitivity of well-folded proteins up to 180 kDa molecular weight.
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    Data for Detection of Exchangeable Protons in NMR Metabolomic Analysis using AI-Designed Water Irradiation Devoid Pulses
    (2025-02-06) Veliparambil Subrahmanian, Manu; Veglia, Gianluigi; Vuckovic, Ivan; Macura, Slobodan; mvelipar@umn.edu; Manu, Veliparambil Subrahmanian; Veglia Lab
    1H NMR spectroscopy has enabled the quantitative profiling of metabolites in various biofluids, emerging as a possible di-agnostic tool for metabolic disorders and other diseases. To boost the signal-to-noise ratio and detect proton resonances near the water signal, current 1H NMR experiments require solvent suppression schemes (e.g., presaturation, jump-and-return, WATERGATE, excitation sculpting, etc.). Unfortunately, these techniques affect the quantitative assessment of analytes containing exchangeable protons. To address this issue, we introduce two new1D 1H NMR techniques that eliminates the water signal, preserving the intensities of exchangeable protons. Using GENETICS-AI, a software that combines an evolutionary algorithm and artificial intelligence, we tailored new WAter irradiation DEvoid (WADE) pulses and optimized 1D 1H NOESY sequence for metabolomics analysis. When applied to human urine samples, kidney tissue extract, and plasma, the WADE technique allowed for accurate measurement of typical metabolites and direct quantification of urea, which is usually challenging to measure using standard NMR experiments. We anticipate that these new NMR techniques will significantly improve the accuracy and reliability of metabolite quantitative assessment for a wide range of biological fluids.
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    Data for Unbiased Clustering of Residues Undergoing Synchronous Motions in Proteins using NMR Spin Relaxation Data
    (2025-02-13) Veliparambil Subrahmanian, Manu; Veglia, Gianluigi; Melacini, Giuseppe; L Kovrigin, Evgenii; Loria, J Patrick; mvelipar@umn.edu; Veliparambil Subrahmanian, Manu; Veglia Lab
    Carr-Purcell-Meiboom-Gill Relaxation Dispersion (CPMG-RD) experiments are highly effective for probing micro- to millisecond conformational exchange processes in proteins. By performing experiments at multiple magnetic field strengths , one can extract dynamic parameters such as exchange rates, population fractions, and chemical shift differences. PySyncDyn is a comprehensive Python-based toolkit that automates the entire workflow from raw data processing to the generation of Dynamic Correlation (SyncDyn) maps. The workflow includes the calculation of effective transverse relaxation rates , pairwise fitting using the Carver-Richards model, generation of correlation maps, and computation of a SyncDyn Score that quantifies the extent of correlated dynamics across the protein. In addition, the Score2Pymol.py script allows visualization of these scores on the three-dimensional structure of the protein in PyMOL.
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    Enhanced Sensitivity of 1H,1H Nuclear Overhauser Effects using Water Irradiation Devoid Pulses
    (2022-09-26) Veliparambil Subrahmanian, Manu; Veglia, Gianluigi; vegli001@umn.edu; Veglia, Gianluigi; Veglia Lab
    The nuclear Overhauser effect (NOE) is one of NMR spectroscopy's most important and versatile parameters. NOE is routinely utilized to determine the structures of medium-to-large size biomolecules and characterize protein-protein, protein-RNA, protein-DNA, and protein-ligand inter-actions. Since NMR studies of biomacromolecules are carried out in aqueous solutions, [1H,1H] NOESY pulse sequences must incorporate water suppression schemes to reduce the water signal that dominates 1H detected experiments. These pulse schemes are also designed to minimize signal intensity losses due to unwanted polarization exchange between water and labile protons. However, at high- and ultra-high magnetic fields, the excitation of the water signal during the execution of the NOESY pulse sequences may cause significant attenuation of NOE cross-peak intensities. Using an evolutionary algorithm coupled with artificial intelligence, we recently designed high-fidelity pulses [Water irrAdiation DEvoid (WADE) pulses] that elude water excitation and irradiate broader bandwidths relative to commonly used pulses. Here, we demonstrate that WADE pulses implemented into the 2D [1H,1H] NOESY experiments increase the intensity of the NOE cross-peaks for labile and, to a lesser extent, non-exchangeable protons. We applied the new [1H,1H] WADE-NOESY pulse sequence to two well-folded medium-size proteins, i.e., the K48C mutant of ubiquitin and the Raf kinase inhibitor protein (RKIP). The new pulse sequence shows a net increase of the NOE intensities varying from 30 to 170% compared to the commonly used NOESY experiments with excitation sculpting sequence as a water suppression element. The new WADE pulses can be easily implemented into 2D and 3D homo- and hetero-nuclear NOESY pulse sequences.
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    GENETICS-AI pulses
    (2022-06-16) Veliparambil Subrahmanian, Manu; Veglia, Gianluigi; vegli001@umn.edu; Veglia, Gianluigi; Gianluigi Veglia Lab
    New RF shapes for applications in Nuclear magnetic resonance. These shapes are in BRUKER format and can be directly used in pulse sequences for biomolecular NMR experiments. We have generated these pulses using a new algorithm called 'GENETICS-AI', which is a combination of an evolutionary algorithm and artificial intelligence. The main advantage of GENETICS-AI is the customizability of RF shape characteristics such as pulse operation, bandwidth, RF inhomogeneity compensation level and fidelity of the operation. The submitted files include broadband universal π/2 and π pulses.
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    High Fidelity GENETICS-AI RF pulses for NMR Spectroscopy and Imaging
    (2022-07-14) Veliparambil Subrahmanian, Manu; vegli001@umn.edu; Gianluigi, Veglia; Gianluigi Veglia Lab
    RF shapes for applications in Nuclear magnetic resonance and Imaging. All the shapes are in BRUKER format and can be directly used in pulse sequences for biomolecular NMR experiments or imaging. All the RF shapes are generated using a new algorithm called 'GENETICS-AI', which is a combination of an evolutionary algorithm and artificial intelligence. The main advantage of GENETICS-AI is the customizability of RF shape characteristics such as pulse operation, bandwidth, RF inhomogeneity compensation level and fidelity of the operation. The submitted files include pulses for inversion, excitation, refocusing with different bandwidths and RF inhomogeneity compensation levels.
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    NMR Pulse Sequences and RF Shapes for RAPID-HMQC
    (2024-02-01) Veliparambil Subrahmanian, Manu; Veglia, Gianluigi; vegli001@umn.edu; Veglia, Gianluigi; Veglia Lab
    The dataset includes radio frequency (RF) shapes and pulse sequences for the RAPID-HMQC nuclear magnetic resonance (NMR) experiment, which were developed using an evolutionary algorithm and artificial intelligence. These novel RF pulses significantly expand the bandwidths for 1H and 15N nuclei and enable the rapid acquisition of spectra.
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    Proton and amide chemical shift list files of wild-type cAMP-dependent protein kinase a (PKA-C) and the chimeric mutant (PKA-JC) and MATLab scripts for the chemical shift analysis
    (2020-11-23) Veglia, Gianluigi; Olivieri, Cristina; Walker, Caitlin; Veliparambil Subrahmanian, Manu; vegli001@umn.edu; Veglia, Gianluigi; University of Minnesota, BMBB Department, Structural Biology Division, Professor Gianluigi Veglia Lab
    Proton and amide chemical shift list files of wild-type cAMP-dependent protein kinase a (PKA-C) and the chimeric mutant (PKA-JC) and MatLab scripts used for the CHESCA and CONCISE analysis. The chemical shift lists were obtained using standard NMR experiments (1H-15N -TROSY-HSQC). The MatLab scripts were used for the CHESCA and CONCISE analysis of the amide chemical shift. These files are part of a publication on Communication biology: "Defective Internal Allosteric Network Imparts Dysfunctional ATP/Substrate Binding Cooperativity in Oncogenic Chimera of Protein Kinase A"
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    The role of the αC-β4 loop in regulating cooperativity interaction in Protein Kinase A
    (2024-02-19) Olivieri, Cristina; Veglia, Gianluigi; Veliparambil Subrahmanian, Manu; Wang, Yingjie; vegli001@umn.edu; Veglia, Gianluigi; Veglia Lab
    This investigation examines the cooperative modulation of Protein Kinase A (PKA) activity by ATP and substrates, with a specialized focus on the enzyme's catalytic subunit (PKA-C), utilizing NMR-restrained molecular dynamics simulations complemented by advanced Markov Model analysis. Herein, we deposit chemical shift datasets for the PKA-C mutant F100A, both in its apo form and in complex with nucleotides and inhibitors, and activity assay data providing a comprehensive insight into the enzyme's allosteric regulation mechanisms.