A5010176069- Protein Structure and Dynamics
- Enzyme Structure and Function
- Electron Spin Resonance Studies
- NMR spectroscopy and applications
- Molecular spectroscopy and chirality
- Advanced NMR Techniques and Applications
- Protein Kinase Regulation and GTPase Signaling
- Mass Spectrometry Techniques and Applications
- Natural Language Processing Techniques
- Biochemical and Structural Characterization
- Viral gastroenteritis research and epidemiology
- Peptidase Inhibition and Analysis
- Image and Signal Denoising Methods
- Spectroscopy Techniques in Biomedical and Chemical Research
- Neuroscience and Neuropharmacology Research
- Spectroscopy and Chemometric Analyses
- Bioinformatics and Genomic Networks
- Animal Virus Infections Studies
- Protein purification and stability
- CCD and CMOS Imaging Sensors
- Modular Robots and Swarm Intelligence
- SARS-CoV-2 detection and testing
- Advanced Memory and Neural Computing
- Toxin Mechanisms and Immunotoxins
- Image Processing Techniques and Applications
Xiamen University
2025
Leidos Biomedical Research Inc. (United States)
2021-2024
Leidos (United States)
2021-2024
Frederick National Laboratory for Cancer Research
2021-2024
Istituto Tecnico Industriale Alessandro Volta
2021
Weatherford College
2021
Center for Cancer Research
2016-2020
National Institutes of Health
2020
National Cancer Institute
2016-2020
University of Minnesota
2011-2017
ABSTRACT The nucleocapsid protein (N) of the severe acute respiratory syndrome coronavirus (SARS-CoV) packages viral genomic RNA and is crucial for viability. However, RNA-binding mechanism poorly understood. We have shown previously that N contains two structural domains—the N-terminal domain (NTD; residues 45 to 181) C-terminal dimerization (CTD; 248 365)—flanked by long stretches disordered regions accounting almost half entire sequence. Small-angle X-ray scattering data show in an...
Eukaryotic protein kinases (EPKs) constitute a class of allosteric switches that mediate myriad signaling events. It has been postulated EPKs' active and inactive states depend on the structural architecture their hydrophobic cores, organized around two highly conserved spines: C-spine R-spine. How spines orchestrate transition enzyme between catalytically uncommitted committed remains elusive. Using relaxation dispersion nuclear magnetic resonance spectroscopy, we found core catalytic...
Engineering and bioconjugation of proteins is a critically valuable tool that can facilitate wide range biophysical structural studies. The ability to orthogonally tag or label domain within multidomain protein may be complicated by undesirable side reactions noninvolved domains. Furthermore, the advantages segmental (or domain-specific) isotopic labeling for NMR, deuteration neutron scattering diffraction, realized an efficient ligation procedure. Common methods—expressed ligation,...
Abstract Localized dynamics of RAS, including regions distal to the nucleotide-binding site, is high interest for elucidating mechanisms by which RAS proteins interact with effectors and regulators designing inhibitors. Among several oncogenic mutants, methyl relaxation dispersion experiments reveal highly synchronized conformational in active (GMPPNP-bound) KRAS G13D , suggests an exchange between two states solution. Methyl 31 P NMR spectra solution confirm a two-state ensemble...
Despite exceptional capabilities, Large Language Models (LLMs) still face deployment challenges due to their enormous size. Post-training structured pruning is a promising solution that prunes LLMs without the need for retraining, reducing computational overhead, and it hardware-deployment friendly. However, training-free nature of post-training leads significant performance degradation. We argue key mitigating this issue lies in accurately determining rate each layer. Meanwhile, we find may...
In this paper, we address the challenge of determining layer-wise sparsity rates large language models (LLMs) through a theoretical perspective. Specifically, identify critical issue ''$\textbf{reconstruction error explosion}$'' in existing LLMs sparsification methods. This refers to cumulative effect reconstruction errors throughout process, where from earlier layers propagate and amplify subsequent layers. As result, overall increases significantly, leading substantial degradation model...
A new computational strategy is reported that provides a fast approximation of numerical solutions differential equations in general. The method demonstrated with the analysis NMR adiabatic relaxation dispersion experiments to reveal biomolecular dynamics. When an analytical solution theoretical describing physical process not available, approach can significantly accelerate speed conventional integration up 105 times. enhanced optimized proton-decoupled pulse sequences, although extremely...
KRAS is the most frequently mutated RAS protein in cancer patients, and it estimated that about 20% of patients United States carried mutant proteins. To accelerate therapeutic development, structures dynamics proteins had been extensively studied by various biophysical techniques for decades. Although 31P NMR studies revealed population equilibrium two major states active GMPPNP-bound form, more complex conformational oncogenic mutants subtly modulate interactions with their downstream...
It is common for NMR relaxation dispersion experiments to suggest an absence of dynamics despite anecdotal indications conformational dynamics. We explore the potential explanations and approaches this conundrum. Some inconsistencies have been observed between two experiments, Carr–Purcell–Meiboom–Gill (CPMG) adiabatic in recent dynamic studies different biomolecules. Theoretical analyses show that such seemingly paradoxical results might come from a complex exchange topology concealed by...
Structural biology often focuses primarily on three-dimensional structures of biological macromolecules, deposited in the Protein Data Bank (PDB). This resource is a remarkable entity for worldwide scientific and medical communities, as well general public, it growing translation into space vast information genomic databases, e.g. GENBANK. There is, however, significantly more to understanding function than co-ordinate ground-state biomolecules. The array biomolecules experiences natural...
Methyl-TROSY is one of the most powerful NMR spectroscopic tools for studying structures and conformational dynamics large protein complexes in solution. In dynamics, side chains usually display heterogeneous including collective local motions, that can be difficult to detect analyze by conventional relaxation dispersion (RD) approaches. The combination NH-based heteronuclear adiabatic (HARD) experiments a geometric approximation (geoHARD) has been shown have several advantages over RD...
The KRAS gene plays a pivotal role in numerous cancers by encoding GTPase that upon association with the plasma membrane activates MAPK pathway, promoting cellular proliferation. In our study, we investigated small molecules disrupt KRAS's interaction, hypothesizing such disruption could turn inhibit mutant RAS signaling. Native mass spectrometry screening of KRAS-FMe identified compounds preference for interacting hypervariable region (HVR), and surface plasmon resonance (SPR) further...
Data-free quantization (DFQ), which facilitates model without real data to address increasing concerns about security, has garnered significant attention within the compression community. Recently, unique architecture of vision transformers (ViTs) driven development specialized DFQ techniques. However, we observe that synthetic images from existing methods suffer deficient semantics issue compared images, thereby compromising performance. Motivated by this, propose SPDFQ, a Semantics...