A5058777008- Protein Structure and Dynamics
- Graphene research and applications
- Nitric Oxide and Endothelin Effects
- Magnetic and transport properties of perovskites and related materials
- Cancer, Hypoxia, and Metabolism
- Computational Drug Discovery Methods
- Parallel Computing and Optimization Techniques
- Quantum and electron transport phenomena
- Enzyme Structure and Function
- Protein Kinase Regulation and GTPase Signaling
- Formal Methods in Verification
- Distributed systems and fault tolerance
- Security and Verification in Computing
- Logic, programming, and type systems
- Imbalanced Data Classification Techniques
- Analytical Chemistry and Chromatography
- Mechanisms of cancer metastasis
- Microbial Natural Products and Biosynthesis
- Metabolism, Diabetes, and Cancer
- Plant biochemistry and biosynthesis
- Rare-earth and actinide compounds
- vaccines and immunoinformatics approaches
- Advanced Condensed Matter Physics
- Sperm and Testicular Function
- RNA and protein synthesis mechanisms
University of Nottingham Ningbo China
2023-2025
Lawrence Livermore National Laboratory
2015-2024
ShanghaiTech University
2024
BridgeBio (United States)
2024
Wenzhou Medical University
2011-2023
Nanjing University of Aeronautics and Astronautics
2012-2023
Shandong University
2020-2023
Zhejiang Academy of Medical Sciences
2017-2022
Hangzhou Medical College
2022
Wenzhou University
2022
Currently the Protein Data Bank (PDB) contains over 25 000 structures that contain a metal ion including Na, Mg, K, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Pd, Ag, Cd, Ir, Pt, Au, and Hg. In general, carrying out classical molecular dynamics (MD) simulations of metalloproteins is convoluted time-consuming process. Herein, we describe MCPB (Metal Center Parameter Builder), which allows one to conveniently rapidly incorporate ions using bonded plus electrostatics model (Hoops et al. J. Am. Chem....
Computational chemists have long demonstrated great interest in finding ways to reliably and accurately predict the molecular properties for transition-metal-containing complexes. This study is a continuation of our validation efforts density functional theory (DFT) methods when applied systems (Riley, K.E.; Merz, K. M., Jr. J. Phys. Chem. 2007, 111, 6044−6053). In previous work we examined DFT using all-electron basis sets, but approaches incorporating effective core potentials (ECPs) are...
Significance Here we present an unprecedented multiscale simulation platform that enables modeling, hypothesis generation, and discovery across biologically relevant length time scales to predict mechanisms can be tested experimentally. We demonstrate our predictive simulation-experimental validation loop generates accurate insights into RAS-membrane biology. Evaluating over 100,000 correlated simulations, show RAS–lipid interactions are dynamic evolving, resulting in: 1) a reordering...
Individual oncogenic KRAS mutants confer distinct differences in biochemical properties and signaling for reasons that are not well understood. activity is closely coupled to protein dynamics regulated through two interconverting conformations: state 1 (inactive, effector binding deficient), 2 (active, enabled). Here we use 31P NMR delineate the populations present wild-type (WT) common (G12C, G12D, G12V, G13D, Q61L) bound its natural substrate GTP or a commonly used nonhydrolyzable analogue...
Abstract The glycine to cysteine mutation on codon 12 of KRAS (KRASG12C) is found in ~15% non-small cell lung cancers and a low percentage colorectal pancreatic adenocarcinomas. This activating pushes the balance cellular towards its active, GTP-bound (ON) state that signals downstream drives proliferation. Recently approved inhibitors KRASG12C bind sequester oncogenic protein inactive GDP-bound (OFF) state, have demonstrated clinical efficacy; however, median duration response has been...
Layered ${\mathrm{Cr}}_{2}{\mathrm{Ge}}_{2}{\mathrm{Te}}_{6}$ is a promising two-dimensional (2D) material for van der Waals bonded ferromagnetic devices since its ferromagnetism can be maintained upon exfoliating the bulk down to few layers. However, magnetic interaction properties and phase-transition type of this system remain controversial. In work, we systematically study critical behavior single crystal. The angle dependence magnetization indicates that has weak anisotropy along $c$...
Computational models can define the functional dynamics of complex systems in exceptional detail. However, many modeling studies face seemingly incommensurate requirements: to gain meaningful insights into some phenomena requires with high resolution (microscopic) detail that must nevertheless evolve over large (macroscopic) length- and time-scales. Multiscale has become increasingly important bridge this gap. Executing multiscale on current petascale computers levels parallelism...
In this Letter, we theoretically explore the physical properties of a new type three-dimensional graphite moir\'e superlattice, bulk alternating twisted (ATG) system with homogeneous twist angle, which is grown by in situ chemical vapor decomposition method. Compared to bilayer graphene (TBG), ATG bestowed an additional wave vector degree freedom due extra dimensionality. As result, when angle smaller than twice magic TBG, there always exist ``magic momenta'' host topological flat bands...
Summary form only given. Conforming to the underlying memory consistency rules is a fundamental requirement for implementing shared systems and developing multiprocessor programs. In order promote understanding enable automated verification, it highly desirable that model specification be both declarative executable. We present framework called Nemos (Nonoperational yet Executable Memory Ordering Specifications), which supports precise automatic execution in same framework. employ uniform...
The class imbalance problem in finance fraud datasets often leads to biased prediction towards the nonfraud class, resulting poor performance class. This study explores effects of utilizing Synthetic Minority Oversampling TEchnique (SMOTE), a Generative Adversarial Network (GAN), and their combinations address issue. Their effectiveness was evaluated using Feed-forward Neural (FNN), Convolutional (CNN), hybrid (FNN+CNN). found that regardless data generation techniques applied, classifier’s...
<div>Abstract<p>Approved inhibitors of KRAS<sup>G12C</sup> prevent oncogenic activation by sequestering the inactive, GDP-bound (OFF) form rather than directly binding and inhibiting active, GTP-bound (ON) form. This approach provides no direct target coverage active protein. Expectedly, adaptive resistance to (OFF)-only is observed in association with increased expression activity KRAS<sup>G12C</sup>(ON). To provide optimal coverage, we have developed...
<p>Supplementary Figure S2 shows the electron density map for BBO-8520 bound to KRAS G12C in GDP and GppNHp states</p>
<p>Supplementary Figure S6 shows that BBO-8520 anti-tumor activity in NCI-H358 CDX sotorasib-resistant tumors</p>
<p>Supplementary Figure S1 shows the Kinact/KI values for BBO-8520, sotorasib and adagrasib in biochemical cell-based assays</p>
<p>Supplementary Material and Methods</p>
<p>Supplementary Figure S5 shows that BBO-8520 demonstrates in vivo pERK inhibition, KRAS G12C target engagement and is well tolerated</p>
<p>Supplementary Figure S3 shows the activity of BBO-8520, sotorasib, and adagrasib on Ba/F3 cells with KRAS G12C mutations altered states GTP hydrolysis</p>
<p>Supplementary Figure S4 summarizes cysteine profiling, RNA-seq and kinomescan studies demonstrating that BBO-8520 is selective for KRAS G12C MAPK inhibition.</p>