A5066822010- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Receptor Mechanisms and Signaling
- Mass Spectrometry Techniques and Applications
- Lipid Membrane Structure and Behavior
- RNA Research and Splicing
- DNA and Nucleic Acid Chemistry
- RNA Interference and Gene Delivery
- Chemokine receptors and signaling
- Supramolecular Self-Assembly in Materials
- Sphingolipid Metabolism and Signaling
- Porphyrin and Phthalocyanine Chemistry
- Monoclonal and Polyclonal Antibodies Research
- Bacterial Genetics and Biotechnology
- Cell Adhesion Molecules Research
- Genomics and Chromatin Dynamics
- Spectroscopy and Quantum Chemical Studies
- Advanced biosensing and bioanalysis techniques
- Antimicrobial Peptides and Activities
- Immunotherapy and Immune Responses
- S100 Proteins and Annexins
- Hormonal and reproductive studies
- Autophagy in Disease and Therapy
- RNA modifications and cancer
- Cellular transport and secretion
Chinese University of Hong Kong, Shenzhen
2019-2025
Chinese University of Hong Kong
2025
Hong Kong University of Science and Technology
2015-2019
University of Hong Kong
2015-2019
Kowloon Hospital
2016-2018
First Affiliated Hospital of Xi'an Jiaotong University
2017
HKUST Shenzhen Research Institute
2015
University of Amsterdam
2011-2013
Amsterdam University of the Arts
2010-2011
KTH Royal Institute of Technology
2007
Abstract MicroRNAs (miRNAs) are noncoding RNAs with 18–26 nucleotides; they pair target mRNAs to regulate gene expression and produce significant changes in various physiological pathological processes. In recent years, the interaction between miRNAs their genes has become one of mainstream directions for drug development. As a large-scale biological database that mainly provides miRNA–target interactions (MTIs) verified by experiments, miRTarBase undergone five revisions enhancements. The...
The last 18 months, or more, have seen a profound shift in our global experience, with many of us navigating once-in-100-year pandemic. To date, COVID-19 remains life-threatening pandemic little to no targeted therapeutic recourse. discovery novel antiviral agents, such as vaccines and drugs, can provide solutions save human beings from severe infections; however, there is specifically effective treatment confirmed for now. Thus, great attention has been paid the use natural artificial...
To achieve the efficient and precise regulation of aggregation-induced emission (AIE), unraveling aggregation effects on amorphous AIE luminogens is vital importance. Using a theoretical protocol combining molecular dynamics simulations quantum mechanics/molecular mechanics calculations, we explored relationship between packing, optical spectra fluorescence efficiency hexaphenylsilole (HPS). We confirmed that redshifted aggregates as compared to crystalline HPS caused by lower packing...
The function of complex biomolecular machines relies heavily on their conformational changes. Investigating these functional changes is therefore essential for understanding the corresponding biological processes and promoting bioengineering applications rational drug design. Constructing Markov State Models (MSMs) based large‐scale molecular dynamics simulations has emerged as a powerful approach to model system with sufficient resolution in both time space. However, rapid development...
Abstract Protein-RNA interaction plays important roles in post-transcriptional regulation. However, the task of predicting these interactions given a protein structure is difficult. Here we show that, by leveraging deep learning model NucleicNet, attributes such as binding preference RNA backbone constituents and different bases can be predicted from local physicochemical characteristics surface. On diverse set challenging RNA-binding proteins, including Fem-3-binding-factor 2, Argonaute 2...
As a critical sphingolipid metabolite, sphingosine-1-phosphate (S1P) plays an essential role in immune and vascular systems. There are five S1P receptors, designated as S1PR1 to S1PR5, encoded the human genome, their activities governed by endogenous S1P, lipid-like mimics, or nonlipid-like therapeutic molecules. Among S1PRs, stands out due its nonredundant functions, such egress of T B cells from thymus secondary lymphoid tissues, making it potential target. However, structural basis...
HMG-CoA reductase (HMGCR) protein is usually upregulated after statin (HMGCR inhibitor) treatment, which inevitably diminishes its therapeutic efficacy, provoking the need for higher doses associated with adverse effects. The proteolysis targeting chimera (PROTAC) technology has recently emerged as a powerful approach inducing degradation. Nonetheless, due to their bifunctional nature, developing orally bioavailable PROTACs remains great challenge. Herein, we identified HMGCR-targeted PROTAC...
Abstract The formyl peptide receptor 1 (FPR1) is primarily responsible for detection of short peptides bearing N-formylated methionine (fMet) that are characteristic protein synthesis in bacteria and mitochondria. As a result, FPR1 critical to phagocyte migration activation bacterial infection, tissue injury inflammation. How distinguishes between non-formyl remains elusive. Here we report cryo-EM structures human FPR1-Gi complex bound S. aureus -derived fMet-Ile-Phe-Leu (fMIFL) E. coli...
CXCR4 binding of its endogenous agonist CXCL12 leads to diverse functions, including bone marrow retention hematopoietic progenitors and cancer metastasis. However, the structure CXCL12-bound remains unresolved despite available structures in complex with antagonists. Here, we present cryoelectron microscopy (cryo-EM) CXCL12-CXCR4-Gi at an overall resolution 2.65 Å. forms a 1:1 stoichiometry CXCR4, following two-site model. The first 8 amino acids mature are crucial for activation by forming...
Argonaute (Ago) proteins and microRNAs (miRNAs) are central components in RNA interference, which is a key cellular mechanism for sequence-specific gene silencing. Despite intensive studies, molecular mechanisms of how Ago recognizes miRNA remain largely elusive. In this study, we propose two-step recognition: selective binding followed by structural re-arrangement. Our model based on the results combination Markov State Models (MSMs), large-scale protein-RNA docking, dynamics (MD)...
Steroid hormones are essential in stress response, immune system regulation, and reproduction mammals. Steroids with 3-oxo-Δ4 structure, such as testosterone or progesterone, catalyzed by steroid 5α-reductases (SRD5As) to generate their corresponding 3-oxo-5α steroids, which for multiple physiological pathological processes. SRD5A2 is already a target of clinically relevant drugs. However, the detailed mechanism SRD5A-mediated reduction remains elusive. Here we report crystal structure...
Chemerin is a processed protein that acts on G protein-coupled receptors (GPCRs) for its chemotactic and adipokine activities. The biologically active chemerin (chemerin 21-157) results from proteolytic cleavage of prochemerin uses C-terminal peptide containing the sequence YFPGQFAFS receptor activation. Here we report high-resolution cryo-electron microscopy (cryo-EM) structure human 1 (CMKLR1) bound to nonapeptide chemokine (C9) in complex with Gi proteins. C9 inserts C terminus into...
Physics-based simulation methods can grant atomistic insights into the molecular origin of function biomolecules. However, potential such approaches has been hindered by their low efficiency, including in design selective agonists where simulations myriad protein–ligand combinations are necessary. Here, we describe an automated input-free path searching protocol that offers (within 14 d using Graphics Processing Unit servers) a minimum free energy (MFEP) defined high-dimension...
Locating the low free energy paths (LFEPs) connecting different conformational states is among major tasks for simulations of complex biomolecules as pathways encode physical essence and, therefore, underlying mechanism their functional dynamics. Finding LFEPs yet challenging due to numerous degrees freedom molecules and expensive force calculations. To alleviate this issue, we have previously introduced a Traveling-Salesman-based Automated Path Searching (TAPS) approach that requires...
The activation of G protein-coupled receptors (GPCRs) is a complex multibody multievent process involving agonist binding, receptor activation, protein coupling, and subsequent activation. order energetics these events, though crucial for the rational design selective GPCR drugs, are challenging to characterize remain largely underexplored. Here, we employed molecular dynamics simulations our recently developed traveling salesman-based automated path searching (TAPS) algorithm efficiently...
Cytokinins are adenine derivatives serving as phytohormones, which essential regulators of plant growth, development, and response to environmental factors. The transport process cytokinins determines their spatial distributions is critical functions. AZA-GUANINE RESISTANT (AZG) family member AZG2 in Arabidopsis thaliana has been identified a cytokinin purine transporter. Here, we characterize the binding towards natural cytokinin, trans-zeatin (tZ), well adenine. structures determined both...
Hydroxycarboxylic acid receptor 1 (HCAR1), also known as lactate or GPR81, is a class A G-protein-coupled with key roles in regulating lipid metabolism, neuroprotection, angiogenesis, cardiovascular function, and inflammatory response humans. HCAR1 highly expressed numerous types of cancer cells, where it participates controlling cell metabolism defense mechanisms, rendering an appealing target for therapy. However, the molecular basis HCAR1-mediated signaling remains poorly understood....
We present an efficient density-based adaptive-resolution clustering method APLoD for analyzing large-scale molecular dynamics (MD) trajectories. performs the k-nearest-neighbors search to estimate density of MD conformations in a local fashion, which can group same high-density region into cluster. greatly improves popular peaks algorithm by reducing running time and memory usage 2–3 orders magnitude systems ranging from alanine dipeptide 370-residue Maltose-binding protein. In addition, we...
Amphiphile self-assembly is an essential bottom-up approach of fabricating advanced functional materials. Self-assembled materials with desired structures are often obtained through thermodynamic control. Here, we demonstrate that the selection kinetic pathways can lead to drastically different self-assembled structures, underlining significance control in self-assembly. By constructing network models from large-scale molecular dynamics simulations, show two largely similar amphiphiles,...
Self-assembly processes play a key role in the fabrication of functional nano-structures with wide application drug delivery and micro-reactors.
Locating the minimum free energy paths (MFEPs) between two conformational states is among most important tasks of biomolecular simulations. For example, knowledge MFEP critical for focusing effort unbiased simulations that are used construction Markov state models to biologically relevant regions system. Typically, existing path searching methods perform local sampling around nodes in a pre-selected collective variable (CV) space allow gradual downhill evolution toward MFEP. Despite wide...
Abstract Despite its functional importance, the molecular mechanism underlying target mRNA recognition by Argonaute (Ago) remains largely elusive. Based on extensive all-atom dynamics simulations, we constructed quasi-Markov State Model (qMSM) to reveal during at position 6-7 in seed region of human 2 (hAgo2). Interestingly, found that slowest mode motion therein is not gRNA-target base-pairing, but coordination phosphate groups with a set positively charged residues hAgo2. Moreover, ability...