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Xiaonan Zhang

Publications and source records attributed to Xiaonan Zhang.

30 records · Page 2Linked to original sources

Unifying Sequences, Structures, and Descriptions for Any-to-Any Protein Generation with the Large Multimodal Model HelixProtX

Proteins are fundamental components of biological systems and can be represented through various modalities, including sequences, structures, and textual descriptions. Despite the advances in deep learning and scientific large language models (LLMs) for protein research, current methodologies predominantly focus on limited specialized tasks -- often predicting one protein modality from another. These approaches restrict the understanding and generation of multimodal protein data. In contrast, large multimodal models have demonstrated potential capabilities in generating any-to-any content like text, images, and videos, thus enriching user interactions across various domains. Integrating these multimodal model technologies into protein research offers significant promise by potentially transforming how proteins are studied. To this end, we introduce HelixProtX, a system built upon the large multimodal model, aiming to offer a comprehensive solution to protein research by supporting any-to-any protein modality generation. Unlike existing methods, it allows for the transformation of any input protein modality into any desired protein modality. The experimental results affirm the advanced capabilities of HelixProtX, not only in generating functional descriptions from amino acid sequences but also in executing critical tasks such as designing protein sequences and structures from textual descriptions. Preliminary findings indicate that HelixProtX consistently achieves superior accuracy across a range of protein-related tasks, outperforming existing state-of-the-art models. By integrating multimodal large models into protein research, HelixProtX opens new avenues for understanding protein biology, thereby promising to accelerate scientific discovery.

cs.LG↗

Pre-Training on Large-Scale Generated Docking Conformations with HelixDock to Unlock the Potential of Protein-ligand Structure Prediction Models

Protein-ligand structure prediction is an essential task in drug discovery, predicting the binding interactions between small molecules (ligands) and target proteins (receptors). Recent advances have incorporated deep learning techniques to improve the accuracy of protein-ligand structure prediction. Nevertheless, the experimental validation of docking conformations remains costly, it raises concerns regarding the generalizability of these deep learning-based methods due to the limited training data. In this work, we show that by pre-training on a large-scale docking conformation generated by traditional physics-based docking tools and then fine-tuning with a limited set of experimentally validated receptor-ligand complexes, we can obtain a protein-ligand structure prediction model with outstanding performance. Specifically, this process involved the generation of 100 million docking conformations for protein-ligand pairings, an endeavor consuming roughly 1 million CPU core days. The proposed model, HelixDock, aims to acquire the physical knowledge encapsulated by the physics-based docking tools during the pre-training phase. HelixDock has been rigorously benchmarked against both physics-based and deep learning-based baselines, demonstrating its exceptional precision and robust transferability in predicting binding confirmation. In addition, our investigation reveals the scaling laws governing pre-trained protein-ligand structure prediction models, indicating a consistent enhancement in performance with increases in model parameters and the volume of pre-training data. Moreover, we applied HelixDock to several drug discovery-related tasks to validate its practical utility. HelixDock demonstrates outstanding capabilities on both cross-docking and structure-based virtual screening benchmarks.

cs.LG↗

HelixFold-Multimer: Elevating Protein Complex Structure Prediction to New Heights

While monomer protein structure prediction tools boast impressive accuracy, the prediction of protein complex structures remains a daunting challenge in the field. This challenge is particularly pronounced in scenarios involving complexes with protein chains from different species, such as antigen-antibody interactions, where accuracy often falls short. Limited by the accuracy of complex prediction, tasks based on precise protein-protein interaction analysis also face obstacles. In this report, we highlight the ongoing advancements of our protein complex structure prediction model, HelixFold-Multimer, underscoring its enhanced performance. HelixFold-Multimer provides precise predictions for diverse protein complex structures, especially in therapeutic protein interactions. Notably, HelixFold-Multimer achieves remarkable success in antigen-antibody and peptide-protein structure prediction, greatly surpassing AlphaFold 3. HelixFold-Multimer is now available for public use on the PaddleHelix platform, offering both a general version and an antigen-antibody version. Researchers can conveniently access and utilize this service for their development needs.

q-bio.BM↗

HelixFold-Single: MSA-free Protein Structure Prediction by Using Protein Language Model as an Alternative

AI-based protein structure prediction pipelines, such as AlphaFold2, have achieved near-experimental accuracy. These advanced pipelines mainly rely on Multiple Sequence Alignments (MSAs) as inputs to learn the co-evolution information from the homologous sequences. Nonetheless, searching MSAs from protein databases is time-consuming, usually taking dozens of minutes. Consequently, we attempt to explore the limits of fast protein structure prediction by using only primary sequences of proteins. HelixFold-Single is proposed to combine a large-scale protein language model with the superior geometric learning capability of AlphaFold2. Our proposed method, HelixFold-Single, first pre-trains a large-scale protein language model (PLM) with thousands of millions of primary sequences utilizing the self-supervised learning paradigm, which will be used as an alternative to MSAs for learning the co-evolution information. Then, by combining the pre-trained PLM and the essential components of AlphaFold2, we obtain an end-to-end differentiable model to predict the 3D coordinates of atoms from only the primary sequence. HelixFold-Single is validated in datasets CASP14 and CAMEO, achieving competitive accuracy with the MSA-based methods on the targets with large homologous families. Furthermore, HelixFold-Single consumes much less time than the mainstream pipelines for protein structure prediction, demonstrating its potential in tasks requiring many predictions. The code of HelixFold-Single is available at https://github.com/PaddlePaddle/PaddleHelix/tree/dev/apps/protein_folding/helixfold-single, and we also provide stable web services on https://paddlehelix.baidu.com/app/drug/protein-single/forecast.

q-bio.BM↗

TCR: A Transformer Based Deep Network for Predicting Cancer Drugs Response

Predicting clinical outcomes to anti-cancer drugs on a personalized basis is challenging in cancer treatment due to the heterogeneity of tumors. Traditional computational efforts have been made to model the effect of drug response on individual samples depicted by their molecular profile, yet overfitting occurs because of the high dimension for omics data, hindering models from clinical application. Recent research shows that deep learning is a promising approach to build drug response models by learning alignment patterns between drugs and samples. However, existing studies employed the simple feature fusion strategy and only considered the drug features as a whole representation while ignoring the substructure information that may play a vital role when aligning drugs and genes. Hereby in this paper, we propose TCR (Transformer based network for Cancer drug Response) to predict anti-cancer drug response. By utilizing an attention mechanism, TCR is able to learn the interactions between drug atom/sub-structure and molecular signatures efficiently in our study. Furthermore, a dual loss function and cross sampling strategy were designed to improve the prediction power of TCR. We show that TCR outperformed all other methods under various data splitting strategies on all evaluation matrices (some with significant improvement). Extensive experiments demonstrate that TCR shows significantly improved generalization ability on independent in-vitro experiments and in-vivo real patient data. Our study highlights the prediction power of TCR and its potential value for cancer drug repurpose and precision oncology treatment.

cs.LG↗

HelixADMET: a robust and endpoint extensible ADMET system incorporating self-supervised knowledge transfer

Accurate ADMET (an abbreviation for "absorption, distribution, metabolism, excretion, and toxicity") predictions can efficiently screen out undesirable drug candidates in the early stage of drug discovery. In recent years, multiple comprehensive ADMET systems that adopt advanced machine learning models have been developed, providing services to estimate multiple endpoints. However, those ADMET systems usually suffer from weak extrapolation ability. First, due to the lack of labelled data for each endpoint, typical machine learning models perform frail for the molecules with unobserved scaffolds. Second, most systems only provide fixed built-in endpoints and cannot be customised to satisfy various research requirements. To this end, we develop a robust and endpoint extensible ADMET system, HelixADMET (H-ADMET). H-ADMET incorporates the concept of self-supervised learning to produce a robust pre-trained model. The model is then fine-tuned with a multi-task and multi-stage framework to transfer knowledge between ADMET endpoints, auxiliary tasks, and self-supervised tasks. Our results demonstrate that H-ADMET achieves an overall improvement of 4%, compared with existing ADMET systems on comparable endpoints. Additionally, the pre-trained model provided by H-ADMET can be fine-tuned to generate new and customised ADMET endpoints, meeting various demands of drug research and development requirements.

q-bio.BM↗

Ultrasensitive refractive index sensor with rotatory biased weak measurement

A modified weak measurement scheme, rotatory biased weak measurement, is proposed to significantly improve the sensitivity and resolution of the refractive index sensor on a total reflection structure. This method introduces an additional phase in the post-selected procedure and generates an extinction point in the spectrum distribution. The biased post-selection makes smaller coupling strength available, which leads to an enhancement of phase sensitivity and refractive index sensitivity. In rotatory biased weak measurement, we achieve an enhanced refractive index sensitivity of 13605 nm/RIU compared to 1644 nm/RIU in standard weak measurement. The performance of sensors with different sensitivity is analyzed, and we find the optimal refractive index resolution of sensors increases with sensitivity. In this work, we demonstrate an optimal refractive index resolution of $4\times10^{-7}$ RIU on a total reflection structure. The rabbit anti-mouse IgG and mouse IgG binding reaction experiments demonstrate that our system has a high response to the concentration of IgG in a wide range and the limit of detection is 15 ng/mL. The improvements in this work are helpful to the optimizations of other optical sensors with weak measurement.

quant-ph↗

Study on MCS Selection and Spectrum Allocation for URLLC Traffic under Delay and Reliability Constraint in 5G Network

To support Ultra-Reliable and Low Latency Communications (URLLC) is an essential character of the 5th Generation (5G) communication system. Unlike the other two use cases defined in 5G, e.g. enhanced Mobile Broadband (eMBB) and massive Machine Type Communications (mMTC), URLLC traffic has strict delay and reliability requirement. In this paper, an analysis model for URLLC traffic is proposed from the generation of a URLLC traffic until its transmission over a wireless channel, where channel quality, coding scheme with finite coding length, modulation scheme and allocated spectrum resource are taken into consideration. Then, network calculus analysis is applied to derive the delay guarantee for periodical URLLC traffic. Based on the delay analysis, the admission region is found under certain delay and reliability requirement, which gives a lower bound on required spectrum resource. Theoretical results in the scenario of a 5G New Radio system are presented, where the SNR thresholds for adaptive modulation and coding scheme selection, transmission rate and delay, as well as admission region under different configurations are discussed. In addition, simulation results are obtained and compared with theoretical results, which validates that the admission region derived in this work provides a lower spectrum allocation bound.

eess.SP↗

Acoustic Pressure Monopole, Velocity Monopole, and Hybrid Monopole

We show that there are two types of acoustic monopoles, namely the pressure monopoles (PMs) and the velocity monopoles (VMs). Under one wave incidence, only the pressure field near a PM at resonance possesses monopolar symmetry, while for a VM at resonance only the velocity field possesses monopolar symmetry. It is the dipolar response function of the monopoles that dictates whether they are PMs or VMs. A hybrid monopolar device with neither velocity nor pressure field symmetry is also demonstrated by combining a VM and a PM, which exhibits two monopole resonances with neither PM nor VM symmetry. The breaking of symmetry could lead to higher absorption of the subwavelength scale devices.

physics.app-ph↗

Wave Manipulations by Coherent Perfect Channeling

We report experimental and theoretical investigations of coherent perfect channeling (CPC), a process that two incoming coherent waves in waveguides are completely channeled into one or two other waveguides with little energy dissipation via strong coherent interaction between the two waves mediated by a deep subwavelength dimension scatterer at the common junction of the waveguides. Two such scatterers for acoustic waves are discovered, one confirmed by experiments and the other predicted by theory, and their scattering matrices are formulated. Scatterers with other CPC scattering matrices are explored, and preliminary investigations of their properties are conducted. The scattering matrix formulism makes it possible to extend the applicable domain of CPC to other scalar waves, such as electromagnetic waves and quantum wavefunctions.

physics.class-ph↗

Acoustic Coherent Perfect Absorbers as Sensitive Null Detectors

We report the experimental realization of acoustic coherent perfect absorption (CPA) of four symmetric scatterers of very different structures. The only conditions necessary for these scatterers to exhibit CPA are that both the reflection and transmission amplitudes of the scatterers are 0.5 under one incident wave, and there are two collinear and counter-propagating incident waves with appropriate relative amplitude and phase. Nearly 1000 times in the modulation of output power has been demonstrated by changing the relative phase of the incident waves over 180°. We further demonstrate that these scatterers are sensitive devices to detect the small differences between two nearly equal incident waves. A 27 % change in the strength of the scattering wave has been demonstrated for every degree of phase deviation from the optimum condition between the incident waves.

physics.class-ph↗

Hybrid membrane resonators for multiple frequency asymmetric absorption and reflection in large waveguide

We report that Hybrid membrane resonators (HMRs) made of a decorated membrane resonator backed by a shallow cavity can function as Helmholtz resonators (HRs) when mounted on the sidewall of a clear waveguide for air ventilation. When two single-frequency HMRs are used in the same scheme as two frequency-detuned HRs, asymmetric total absorption/reflection is demonstrated at 286.7 Hz with absorption coefficient over 97 % in a waveguide 9 cm x 9 cm in cross section. When two multiple-frequency HMRs are used, absorption in the range of near 60 % to above 80 % is observed at 403 Hz, 450 Hz, 688 Hz, 863 Hz and 945 Hz. Theoretical predictions agree well with the experimental data. The HMRs may replace HRs in duct noise reduction applications in that at a single operation frequency they have stronger strength to cover a much larger cross section area than that of HRs with similar cavity volume, and they can be designed to provide multiple frequency absorption band.

physics.class-ph↗