The αC-β4 loop controls the allosteric cooperativity between nucleotide and substrate in the catalytic subunit of protein kinase A.

Allosteric cooperativity between ATP and substrates is a prominent characteristic of the cAMP-dependent catalytic subunit of protein kinase A (PKA-C). This long-range synergistic action is involved in substrate recognition and fidelity, and it may also regulate PKA's association with regulatory subunits and other binding partners. To date, a complete understanding of this intramolecular mechanism is still lacking.

AI-designed RF pulses enable fast pulsing heteronuclear multiple quantum coherence NMR experiment at high and ultra-high magnetic fields.

We present a new AI-optimized 2D heteronuclear multiple quantum coherence (RAPID-HMQC) pulse sequence for NMR spectroscopy. RAPID-HMQC is a longitudinal H relaxation-optimized experiment with new AI-designed band-selective pulses to accelerate the analysis of organic compounds, metabolites, biopolymers, and real-time monitoring of dynamic processes at high- and ultra-high magnetic fields.

An NMR portrait of functional and dysfunctional allosteric cooperativity in cAMP-dependent protein kinase A.

The cAMP-dependent protein kinase A (PKA) is the archetypical eukaryotic kinase. The catalytic subunit (PKA-C) structure is highly conserved among the AGC-kinase family. PKA-C is a bilobal enzyme with a dynamic N-lobe, harbouring the Adenosine-5'-triphosphate (ATP) binding site and a more rigid helical C-lobe.

High-fidelity control of spin ensemble dynamics via artificial intelligence: from quantum computing to NMR spectroscopy and imaging.

High-fidelity control of spin ensemble dynamics is essential for many research areas, spanning from quantum computing and radio-frequency (RF) engineering to NMR spectroscopy and imaging. However, attaining robust and high-fidelity spin operations remains an unmet challenge. Using an evolutionary algorithm and artificial intelligence (AI), we designed new RF pulses with customizable spatial or temporal field inhomogeneity compensation.

CHESPA/CHESCA-SPARKY: automated NMR data analysis plugins for SPARKY to map protein allostery.

Motivation: Correlated Nuclear Magnetic Resonance (NMR) chemical shift changes identified through the CHEmical Shift Projection Analysis (CHESPA) and CHEmical Shift Covariance Analysis (CHESCA) reveal pathways of allosteric transitions in biological macromolecules. To address the need for an automated platform that implements CHESPA and CHESCA and integrates them with other NMR analysis software packages, we introduce here integrated plugins for NMRFAM-SPARKY that implement the seamless detection and visualization of allosteric networks.

Availability And Implementation: CHESCA-SPARKY and CHESPA-SPARKY are available in the latest version of NMRFAM-SPARKY from the National Magnetic Resonance Facility at Madison (http://pine.

Simultaneous detection of intra- and inter-molecular paramagnetic relaxation enhancements in protein complexes.

Paramagnetic relaxation enhancement (PRE) measurements constitute a powerful approach for detecting both permanent and transient protein-protein interactions. Typical PRE experiments require an intrinsic or engineered paramagnetic site on one of the two interacting partners; while a second, diamagnetic binding partner is labeled with stable isotopes (N or C). Multiple paramagnetic labeled centers or reversed labeling schemes are often necessary to obtain sufficient distance restraints to model protein-protein complexes, making this approach time consuming and expensive.