Biology subjects

Li, A.

Publications and source records attributed to Li, A..

At least 91 records · Page 5Linked to original sources

bioRxiv2025

Cell type-specific contributions to impaired blood-brain barrier and cerebral metabolism in presymptomatic 5XFAD mice

Altered cerebral metabolism and blood-brain barrier (BBB) dysfunction are emerging as critical contributors to the preclinical phase of Alzheimers disease (AD), underscoring their role in early pathogenesis. To identify sensitive biomarkers before irreversible neuronal loss and cognitive decline, we examined 5XFAD mice at 3 months of age by applying multiple advanced MRI techniques. Arterial spin tagging based MRI revealed increased BBB permeability and water extraction fraction, indicating compromised BBB integrity at the early stage of pathogenesis in 5xFAD mice. Despite preserved cerebral blood flow, a decreased unit mass cerebral metabolic rate of oxygen (CMRO2) was evident in the same cohorts of 5XFAD mice. Interestingly, a region-specific decrease of tissue pH values was detected in the hippocampus of these 5XFAD mice by creatine chemical exchange saturation transfer MRI. Elevated neuronal H4K12 lactylation in the hippocampus supports the reduced pH values. To further dissect the cellular and molecular mechanisms underlying these MRI-detectable changes in 5XFAD mice, we conducted single-nucleus RNA sequencing (snRNA-Seq) with optimized blood vessel enrichment protocols. Our results revealed cell type-specific transcriptomic changes in the hippocampus of 3-month-old 5XFAD mice, including downregulation of synaptogenesis and synaptic transmission genes in the CA1 and dentate gyrus excitatory neurons, impaired endothelial gene expression linked to brain barrier function and angiogenesis, altered innate immune response genes in astrocytes, as well as upregulation of cholesterol biosynthesis and metabolism genes in the CA1 excitatory neurons. These findings underlie the intricate interplay between BBB disruption and metabolic dysregulation before the onset of cognitive decline in AD. Our study demonstrates that BBB dysfunction and cerebral metabolic alterations preceded brain hypoperfusion and cognitive decline, emphasizing potential molecular pathways for early intervention. These findings, once validated in human studies, could significantly enhance early diagnosis and inform novel therapeutic strategies targeting early AD pathogenesis.

neuroscience↗

bioRxiv2025

A Continuously Oxygenated Macroencapsulation System Enables High-Density Packing and Delivery of Insulin-Secreting Cells

The encapsulation of insulin-secreting cells within immuno-protective systems holds significant promise for curative treatment of type 1 diabetes without immunosuppression. A major challenge, however, remains the inadequate oxygen tension within the encapsulation systems, which compromises the survival and function of encapsulated cells and necessitates low packing density and impractically large systems to deliver a curative cell mass. In this study, we present a novel cell encapsulation system capable of generating oxygen via the electrolysis of tissue moisture to provide a continuous oxygen supply to densely packed insulin-secreting cells. Our system comprises a miniaturized implantable electrochemical oxygen generator (iEOG) and a scalable cylindrical cell encapsulation pouch, designed in a linear configuration to facilitate minimally invasive implantation and retrieval. The oxygen generation from the system was shown to be precisely controlled, stable, and capable of supporting clinically relevant doses of pancreatic islets. In vitro studies demonstrated that the oxygenated system effectively maintained the viability and function of insulinoma cell aggregates and human pancreatic islets at densities of 60,000 islet equivalents per mL (IEQ/mL) or 4,200 IEQ/cm{superscript 2} under a hypoxic cell culture condition (1% O ). In an allogeneic rat model, the oxygenated systems containing pancreatic islets implanted into the poorly vascularized but clinically attractive subcutaneous space at a density of 60,000 IEQ/mL successfully reversed diabetes for up to about 3 months without the need for immunosuppression, while animals implanted with non-oxygenated systems remained diabetic. Most ([~] 90%) of the pancreatic islets encapsulated in the continuously oxygenated systems were found viable and functional upon retrieval. These findings suggest the feasibility of using continuous oxygenation to support insulin-secreting cells at high loading densities in subcutaneous space, enabling the development of an encapsulation system with clinically practical dimensions.

bioengineering↗

bioRxiv2025

Amplicon sequencing detects, identifies, and quantifies minority variants in mixed-species infections of Cryptosporidium parasites

Cryptosporidium is a globally endemic parasite genus with over 40 recognized species. While C. hominis and C. parvum are responsible for most human infections, human cases involving other species have also been reported. Furthermore, there is increasing evidence of simultaneous infections with multiple species. Therefore, we devised a new means to identify various species of Cryptosporidium in mixed infections by sequencing a 431 bp amplicon of the 18S rRNA gene encompassing two variable regions. Using the DADA2 pipeline, amplicons were first identified to a genus using the SILVA 132 reference database; then Cryptosporidium amplicons to a species using a custom database. This approach demonstrated sensitivity, successfully detecting and accurately identifying as little as 0.001 ng of C. parvum DNA in a complex stool background. Notably, we differentiated mixed infections and demonstrated the ability to identify potentially novel species of Cryptosporidium both in situ and in vitro. Using this method, we identified Cryptosporidium parvum in Egyptian rabbits with three samples showing minor mixed infections. By contrast, no mixed infections were detected in Egyptian children, who were primarily infected with C. hominis. Thus, this pipeline provides a sensitive tool for Cryptosporidium species-level identification, allowing for the detection and accurate identification of minor variants and mixed infections.

microbiology↗

bioRxiv2025

A multi-institutional investigation of psilocybin's effects on mouse behavior

Studies reporting novel therapeutic effects of psychedelic drugs are rapidly emerging. However, the reproducibility and reliability of these findings could remain uncertain for years. Here, we implemented a multi-institutional collaborative approach to define the robust and replicable effects of the psychedelic drug psilocybin on mouse behavior. Five laboratories performed the same experiments to test the acute and persistent effects of psilocybin (2 mg/kg, IP) on various behaviors that psychedelics have been proposed to affect, including anxiety-related approach-avoidance, exploration, sociability, depression-related behaviors, fear extinction, and social reward learning. Through this coordinated approach, we found that psilocybin had several robust and replicable acute effects on mouse behavior, including increased anxiety- and avoidance-related behaviors and decreased fear expression. Surprisingly, however, we found that psilocybin did not have replicable effects 24 hours post psilocybin administration on reducing anxiety- and depression-like behaviors or facilitating fear extinction learning. Additionally, we were unable to observe psilocybin-induced alterations in social preference or social reward learning. Overall, our comprehensive characterization of psilocybins acute and persistent behavioral effects using [~]200 total male and female mice per experiment spread across five independent labs demonstrates with unique certainty several acute drug effects and suggests that psilocybins persistent effects in mice may be more modest and inconsistent than previously suggested. We believe this unusual multi-laboratory, highly coordinated research effort serves as a model for facilitating the generation of replicable results and consequently will reduce efforts based on unreliable and spurious results.

neuroscience↗

bioRxiv2025

Injectable adhesive hydrogel-drug complexes synchronize the release of chemoimmunotherapy to treat brain tumors in mice

Brain tumor therapy remains limited by an immunosuppressive, monotherapy-resistant tumor microenvironment and by a paucity of technologies capable of controlling therapy delivery kinetics to the tumor. Here, we describe tissue-adhesive hydrogel-drug complexes (HDCs) for the controlled release of combination therapies synchronized with immune cycle responses following intracranial administration. Injected adhesive HDCs enabled the controlled co-delivery of multiple payloads (chemotherapy, stimulator of interferon genes agonist cyclic dinucleotide nanoparticles, immune checkpoint blockade antibodies), leading to enhanced long-term survival (>80%) and protection from contralateral hemisphere rechallenge after a single dose in multiple syngeneic orthotopic glioblastoma mouse models. Mechanistic studies revealed that tumor rejection is a consequence of reprogramming the tumor microenvironment, driven by three key phases: the initial rapid expression of inflammatory cytokines, notably IFN-{gamma}, and tumor sensitization with antigen exposure during chemoimmunotherapy release, followed by the recruitment and subsequent sustained activation of antigen-presenting and effector cells facilitated by the hydrogels multiweek delivery period. These findings point to tissue-adhesive HDCs, and therapeutic release synchronized with biological responses as key considerations for realizing robust immune activation without provoking toxicity in the treatment of solid tumors.

bioengineering↗

bioRxiv2025

Accumbal cholinergic interneurons regulate decision making or motor impulsivity depending on latent task state

Dopaminergic transmission within the nucleus accumbens is broadly implicated in risk/reward decision making and impulse control, and the rat gambling task (rGT) measures both behaviours concurrently. While the resulting indices of risky choice and impulsivity correlate at the population level, dopaminergic manipulations rarely impact both behaviours uniformly, with changes in choice more likely when dopaminergic transmission is altered during task acquisition. Although the task structure of the rGT remains constant, the importance of accumbal dopamine signals relevant for reward prediction versus impulse control may vary over time; the former should dominate while learning which option maximises sugar pellet profits, while the suppression of premature responses becomes more valuable once a decision-making strategy is set and can be exploited. Cholinergic interneurons (CINs) critically control dopamine release within the striatum, and can also encode latent task states deciphered by the frontal cortex. We theorised that aCINs may set the dopaminergic tone of the accumbens to maximise reward learning or impulse control during task acquisition or performance, respectively. Using chemogenetics, we found some support for this hypothesis: activation and inhibition of aCINs once behaviour was stable increased and decreased motor impulsivity in both sexes but had no effect on choice patterns. In contrast, activating and inhibiting aCINs throughout task acquisition did not alter motor impulsivity, but decreased and increased risky choice respectively. However, the former effect was only seen in males and the latter in females. We conclude by proposing a set of testable predictions regarding interactions between acetylcholine and dopamine that could explain these sex differences.

animal behavior and cognition↗

bioRxiv2025

The first chromosomal-level genome assembly of an allotetraploid oyster

Tetraploid oysters are used to cross with diploids to produce triploid oysters that have become an important part of the oyster aquaculture industry worldwide. Although most tetraploid oysters are artificially induced autotetraploids, allotetraploids can be produced between closely related species, providing new opportunities for polyploid breeding and studying genome interactions. Using PacBio sequencing, Illumina sequencing, and high-throughput chromosome conformation capture scaffolding, we assembled the first high-quality genome assembly of an artificially induced allotetraploid between the Pacific oyster Crassostrea gigas and Portuguese oyster Crassostrea angulata. The assembled genome is 1.23 Gb, with a contig N50 of 2.56 Mb and a scaffold N50 of 57.22 Mb, and anchored to 20 chromosomes. The assembly contains 58,330 protein-coding genes, 98.34% of which are functionally annotated. The heterozygosity and the ratio of repetitive sequences is 5.50% and 46.43%, respectively. This chromosomal-level genome assembly of an allotetraploid oyster provides a valuable genetic resource for studying genome biology of molluscs and for advanced breeding of polyploids that are critical for the oyster aquaculture industry.

genomics↗

bioRxiv2025

PLXNB1 and other signaling drives a pathologic astrocyte state contributing to cognitive decline in Alzheimer's Disease

Alzheimers disease (AD) is marked by the coordinated emergence of disease-associated cell states across multiple cell types. Here, we first performed a meta-analysis of single-nucleus transcriptomic (snRNAseq) data from 869 brains of diverse decedents, confirming the critical role of an SLC38A2highSMTNhighCACNA1Dhighastrocyte subset, Astrocyte 10 (Ast10), in AD and aging-related cognitive decline. We then investigated the signaling drivers of Ast10s emergence in the aging brain, focusing on interactions among microglial and astrocytic subsets. Analysis of the snRNAseq data prioritized a set of ligands and receptors that are robustly predictive of Ast10 proportions across participants, and we confirm our predictions in multiple studies. Independent validation with spatial transcriptomics reveals striking colocalization of these prioritized ligands with the Ast10 signature in AD brain tissue, but not with other astrocytic states. Genetic ablation of a top receptor PLXNB1 in murine and human iPSC-derived astrocytes decreased the Ast10 signature, confirming its regulatory role. Finally, we find that Ast10 may contribute to cognitive decline through synaptic loss and is associated with cognitive decline independent of AD. Thus, Ast10 and its regulators are potential points of convergence for multiple neurodegenerative mechanisms and may be promising targets for therapeutic development to preserve cognitive function.

neuroscience↗

bioRxiv2025

Somatic repetitive element insertions Define New Biomarkers in Pan-cancer genome

Repetitive elements insertions (REIs), including tandem repeat insertions (TRIs) and transposable element insertions (TEIs), constitute >90% of large-scale (>50bp) somatic insertions and are linked to diseases and cancer biomarkers. However, the genomic landscape of large-scale REIs in pan-cancer has not been well-characterized due to short-read sequencing limitations. Here, we detected somatic REIs in 325 cancer genomes across 12 cancer types using long-read whole-genome sequencing and customized algorithms. The diverse sequence patterns of somatic TRIs and the insertion mechanisms of somatic TEIs were characterized across different cancer types. We identified 152 high-frequency somatic TRIs, with 10 showing pan-cancer characteristics, including TRIs in SHROOM2, PALMD, and the enhancer of PTPRZ1. The MHC class II gene cluster exhibited the highest somatic TEI abundance, affecting [~]40% tumors. Adenocarcinomas and squamous cell carcinomas exhibited differing TEI distributions within this region. Our study highlights REIs as important but under-explored markers for personalized cancer diagnosis and immunotherapy.

genomics↗

bioRxiv2025

The Sequential Multispecies Coalescent

The multispecies coalescent (MSC) model applies coalescent theory to gene evolution within and among reproductively isolated populations ("species") to estimate a species tree in the face of gene tree conflict resulting from deep coalescence. Sequential Monte Carlo (SMC) uses particle filtering to sample a posterior distribution, providing a fully-Bayesian and easily parallelized alternative to traditional MSC tree inference approaches. The method we propose samples first from the joint posterior distribution of gene and species trees, then samples species trees conditional on gene trees sampled previously, employing SMC for both rounds. Analyses of simulated and empirical datasets yield results comparable to state-of-the-art Bayesian MCMC approaches. Sampling the multispecies coalescent using SMC retains the advantages of fully Bayesian methods and is parallelizable in ways that Bayesian MCMC methods are not but also adds unique challenges. We demonstrate the performance of SMC compared to other commonly-used species tree methods using two empirical datasets and 400 simulated datasets.

evolutionary biology↗

bioRxiv2025

Neuropixels Opto: Combining high-resolution electrophysiology and optogenetics

High-resolution extracellular electrophysiology is the gold standard for recording spikes from distributed neural populations, and is especially powerful when combined with optogenetics for manipulation of specific cell types with high temporal resolution. We integrated these approaches into prototype Neuropixels Opto probes, which combine electronic and photonic circuits. These devices pack 960 electrical recording sites and two sets of 14 light emitters onto a 70 m wide, 1 cm long shank, allowing spatially addressable optogenetic stimulation with blue and red light. In mouse cortex, Neuropixels Opto probes delivered high-quality recordings together with spatially addressable optogenetics, differentially activating or silencing neurons at distinct cortical depths. In mouse striatum and other deep structures, Neuropixels Opto probes delivered efficient optotagging, facilitating the identification of two cell types in parallel. Neuropixels Opto probes represent an unprecedented tool for recording, identifying, and manipulating neuronal populations.

neuroscience↗

bioRxiv2025

TransBrain: A computational framework for translating brain-wide phenotypes between humans and mice

Despite remarkable advances in whole-brain imaging technologies, the lack of quantitative approaches to bridge rodent preclinical and human studies remains a critical challenge. Here we present TransBrain, a computational framework enabling bidirectional translation of brain-wide phenotypes between humans and mice. TransBrain improves human-mouse homology mapping accuracy through: (1) a novel detached region-specific deep neural network trained on integrated multi-modal human transcriptomics to improve cortical correspondence (89.5% improvement over the original transcriptome), which revealed two evolutionarily conserved gradients explaining >50% of cortical organizational variance, and (2) random walk-based graph representation learning to construct a unified cross-species latent space incorporating anatomical hierarchies and structural connectivity. We demonstrated TransBrains utility through three cross-species applications: quantitative assessment of resting-state brain organizational features, inferring human cognitive functions from mouse optogenetic circuits, and translating molecular insights from mouse models to individual-level mechanisms in autism. TransBrain enables quantitative cross-species comparison and mechanistic investigation of both normal and pathological brain functions.

neuroscience↗

bioRxiv2025

Single-cell spatial transcriptome reveals pathological features of human hippocampus with sclerosis

More than half of epileptic patients ultimately turned to intractable epilepsy. Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), the most common type of intractable epilepsies, whose pathological mechanism remains elusive. Here, using 42 human hippocampal samples from surgical donors of MTLE (32 with and 10 without HS) through single-cell resolution Stereo-seq and histologcial experiments, we revealed spatially pathological changes of gene expression and cell type composition with HS systematically. After precise parcellation of hippocampal subregions and differentially expressed gene (DEG) analysis between each region with and without sclerosis, we found Cornu Ammonis (CA) subregions with higher number of DEGs were vulnerable to sclerosis, especially CA1 and CA3. Within CA1, we found that CA1-superficial and proximal areas were more vulnerable than CA1-deep and distal areas in sclerosis. Meanwhile, after analyzing 350,795 segmented cells from Stereo-seq, we found dramatically increasing density of astrocyte accompanied with significantly decreasing density of excitatory neurons in CA1, especially superficial and proximal CA1, and CA3 in sclerosis. In these two vulnerable subregions, proliferative astrocyte (P_astrocyte) and reactive astrocyte (R_astrocyte) were found to be enriched whereas apoptotic subtype of astrocyte (A_astrocyte), related with apoptotic pathway, was mainly located in alveus, which strengthened cell communication with reactive microglia (R_microglia) in HS, revealing the novel pathological feature in our work. The pseudotime analysis indicated that CA excitatory neurons underwent synaptic impairment, energy dysfunction, aging, and finally losing cell identity until death through autophagy or apoptosis. Besides, we also found a resilient subtype, EX_CA2-4.3, highly expressed extracellular matrix related genes including PDYN, and was increasing the interaction of BDNF-NTRK, NFASC-CNTN1 to withstand the damage from sclerosis. Together, our study provided a reference of human hippocampus with and without HS caused by MTLE, and highlighted the potential pathological mechanism on molecular and cellular level of MTLE-HS.

neuroscience↗

bioRxiv2025

Food pairing independently associated with cardiometabolic traits beyond dietary patterns across western and eastern populations

Cardiometabolic health is closely linked to diet. Both specific food choices and dietary indices are commonly used to guide cardiometabolic protection strategies. However, the balance between foods may also significantly impact cardiometabolic health. Here, we explore the balance and imbalance in long-term dietary food intake to quantify food pairing patterns (FPs), providing insights beyond conventional dietary indices and single-food intake frequencies. Using data from our GGMP (n = 6,994) and the NHANES (n = 7,350) cohorts, we observed that long-term food pairing patterns are independent of single food intake frequency and dietary indices. We identified 1,759 and 306 cardiometabolic-related long-term food pairing patterns from two cohorts (FDR < 0.05), respectively. Notably, around 80% of these pairing foods not individually associated with cardiometabolic traits, and food pairing pattern associations with cardiometabolic traits at hyper food group level were consistent across Eastern and Western populations. Besides, mediation analysis revealed that 72.7% of long-term food pairing patterns affected cardiometabolic traits through 31 microbial genera, with Clostridiumsensustricto1 playing a predominant role. Moreover, multi-step mediation analysis found that microbes mediated the impact of long-term food pairing patterns on cardiometabolic traits primarily through their metabolic pathways, such as pyruvate fermentation to propanoate and ergothioneine biosynthesis pathways. Our data suggest that balance between dietary foods is broadly associated with cardiometabolic traits by modulating gut microbial functionalities, in contrast to the lower occurrence when considering individual foods in isolation. These results offer a novel perspective for designing personalized dietary strategies beyond present dietary indices to enhance cardiometabolic health.

microbiology↗

bioRxiv2025

FGF12A Regulates Nav1.5 via CaM-regulated and CaM-independent Mechanisms

Opening of the cardiac voltage-gated Na+ channel (Nav1.5) is responsible for robust depolarization of the cardiac action potential, while inactivation, which rapidly follows, allows for repolarization. Regulation of both the voltage- and time-dependent kinetics of Nav1.5 inactivation can alter the ability of the heart to initiate and sustain a re-entrant arrhythmia. The C-terminal domain (CTD) of Nav1.5 has been shown to modulate fast inactivation of the channel, and multiple auxiliary proteins bind to the CTD, including calmodulin (CaM) and intracellular fibroblast growth factor 12A (FGF12A). Recently, a non-canonical CaM-binding site was also discovered on the N-terminal of A-splice variants of iFGFs. We performed cut-open Vaseline gap (COVG) voltage-clamp to test whether FGF12A with and without CaM regulates Nav1.5 gating. In WT Nav1.5 channels, FGF12A with and without CaM present had a minimal effect on the voltage dependence of both activation and inactivation. Conversely, when CaM is absent on the Nav1.5 CTD (IQ/AA), a dramatic shift in steady-state inactivation (SSI) occurred, regardless of whether CaM was present on FGF12A. These two distinct mechanisms are operative in Nav1.5 LQT3 mutations where FGF12A requires CaM to shift in the voltage-dependence of inactivation, but not to inhibit the persistent late current. We conclude that there are two distinct mechanisms by which FGF12A modulates the Nav1.5 channel: CaM-regulated alteration of the voltage dependence of inactivation and CaM-independent inhibition of persistent late current.

biophysics↗

bioRxiv2024

Structural basis of phosphate export by human XPR1

Phosphate is essential for all life forms because of its indispensable roles in energy metabolism, nucleic acid and phospholipid synthesis, cellular signaling, and the formation of bones and teeth. Its homeostasis is maintained through balanced import and export processes. In humans, XPR1 has been proposed as the sole phosphate exporter, although some controversy remains. Here, we report the closed and open structures of human XPR1, purified in the absence and presence of exogenous InsP6, respectively. The exporter forms a symmetric homodimer, with transmembrane helix (TM) 1 serving as the dimeric interface. The transmembrane domain of each protomer contains a transport module (TM5-10) and a supporting module (TM1-4). Compared to the closed XPR1, the open structure demonstrates a significant displacement of the extracellular portion of TM9 towards the periphery of the phosphate transport pathway, creating an open portal to the extracellular milieu. Additionally, a potential phosphate ion coordination site is strategically located in the middle of the transport pathway. On the intracellular side, the pathway entrance is obstructed by a cluster of residues, the C-plug, positioned on the carboxyl side of TM10. Consistently, the removal of the C-terminus significantly increases the transport activity of XPR1 in reconstituted liposomes. Our findings provide a comprehensive understanding of the export mechanism of human XPR1 and hold promise for the development of potential therapeutics for primary familial brain calcification and ovarian cancer.

biochemistry↗

bioRxiv2024

Ilastik: a machine learning image analysis platform to interrogate stem cell fate decisions across multiple vertebrate species

Stem cells are the key cellular source for regenerating tissues and organs in vertebrate species. Historically, the investigation of stem cell fate decisions in vivo has been assessed in tissue sections using immunohistochemistry (IHC), where a trained user quantifies fluorescent signal in multiple randomly selected images using manual counting--which is prone to inaccuracies, bias, and is very labor intensive. Here, we highlight the performance of a recently developed machine-learning (ML)-based image analysis program called Ilastik using skeletal muscle as a model system. Interestingly, we demonstrate that Ilastik accurately quantifies Paired Box Protein 7 (PAX7)-positive muscle stem cells (MuSCs) before and during the regenerative process in whole muscle sections from mice, humans, axolotl salamanders, and short-lived African turquoise killifish, to a precision that exceeds human capabilities and in a fraction of the time. Overall, Ilastik is a free user-friendly ML-based program that will expedite the analysis of stained tissue sections in vertebrate animals.

cell biology↗

bioRxiv2024

Electron-density informed effective and reliable de novo molecular design and lead optimization with ED2Mol

Generative drug design opens new avenues for discovering novel compounds within the vast chemical space rather than conventional screening against limited compound libraries. However, the practical utility of the generated molecules is frequently constrained, as many designs prioritize a narrow range of pharmacological properties while neglecting physical reliability, which hinders the success rate of subsequent wet-lab evaluations. To address this, we propose ED2Mol, a deep learning-based approach that leverages fundamental electron density information to improve de novo molecular generation and lead optimization. The extensive evaluations across multiple benchmarks demonstrate that ED2Mol surpasses existing methods in terms of generation success rate and >97% physical reliability. It also facilitates automated lead optimization that is not fully implemented by other methods using fragment-based strategies. Furthermore, ED2Mol exhibits generalizability to more challenging, unseen allosteric pocket benchmarks, attaining consistent performance in both de novo molecule generation and lead optimization. More importantly, ED2Mol has been applied to various real-world essential targets, successfully identifying wet-lab validated bioactive compounds, ranging from FGFR3 orthosteric inhibitors to CDC42 allosteric inhibitors and GCK allosteric activators. The directly generated binding modes of these compounds with target proteins are close to predictions through molecular docking and further validated via the X-ray co-crystal structure. All these results highlight ED2Mols potential as a useful tool in realistic drug design with enhanced effectiveness, physical reliability, and practical applicability.

bioinformatics↗