Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Spatiotemporal identification of druggable binding sites using deep learning.

ABSTRACT: Identification of novel protein binding sites expands druggable genome and opens new opportunities for drug discovery. Generally, presence or absence of a binding site depends on the three-dimensional conformation of a protein, making binding site identification resemble the object detection problem in computer vision. Here we introduce a computational approach for the large-scale detection of protein binding sites, that considers protein conformations as 3D-images, binding sites as objects on these images to detect, and conformational ensembles of proteins as 3D-videos to analyze. BiteNet is suitable for spatiotemporal detection of hard-to-spot allosteric binding sites, as we showed for conformation-specific binding site of the epidermal growth factor receptor, oligomer-specific binding site of the ion channel, and binding site in G protein-coupled receptor. BiteNet outperforms state-of-the-art methods both in terms of accuracy and speed, taking about 1.5 minutes to analyze 1000 conformations of a protein with ~2000 atoms.

SUBMITTER: Kozlovskii I

PROVIDER: S-EPMC7591901 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Spatiotemporal identification of druggable binding sites using deep learning.

Kozlovskii Igor I Popov Petr P

Communications biology 20201027 1

Identification of novel protein binding sites expands druggable genome and opens new opportunities for drug discovery. Generally, presence or absence of a binding site depends on the three-dimensional conformation of a protein, making binding site identification resemble the object detection problem in computer vision. Here we introduce a computational approach for the large-scale detection of protein binding sites, that considers protein conformations as 3D-images, binding sites as objects on t ...[more]

PMID: 33110179

Similar Datasets

Identification of RNA pseudouridine sites using deep learning approaches.

Project description:Pseudouridine(Ψ) is widely popular among various RNA modifications which have been confirmed to occur in rRNA, mRNA, tRNA, and nuclear/nucleolar RNA. Hence, identifying them has vital significance in academic research, drug development and gene therapies. Several laboratory techniques for Ψ identification have been introduced over the years. Although these techniques produce satisfactory results, they are costly, time-consuming and requires skilled experience. As the lengths of RNA sequences are getting longer day by day, an efficient method for identifying pseudouridine sites using computational approaches is very important. In this paper, we proposed a multi-channel convolution neural network using binary encoding. We employed k-fold cross-validation and grid search to tune the hyperparameters. We evaluated its performance in the independent datasets and found promising results. The results proved that our method can be used to identify pseudouridine sites for associated purposes. We have also implemented an easily accessible web server at http://103.99.176.239/ipseumulticnn/.

| S-EPMC7901771 | biostudies-literature

In Silico Identification of Potential Druggable Binding Sites on CIN85 SH3 Domain.

Project description:Protein-protein interactions (PPIs) play a pivotal role in the regulation of many physiological processes. The dysfunction of some PPIs interactions led to the alteration of different biological pathways causing various diseases including cancer. In this context, the inhibition of PPIs represents an attractive strategy for the design of new antitumoral agents. In recent years, computational approaches were successfully used to study the interactions between proteins, providing useful hints for the design of small molecules able to modulate PPIs. Targeting PPIs presents several challenges mainly due to the large and flat binding surface that lack the typical binding pockets of traditional drug targets. Despite these hurdles, substantial progress has been made in the last decade resulting in the identification of PPI modulators where some of them even found clinical use. This study focuses on MUC1-CIN85 PPI which is involved in the migration and invasion of cancer cells. Particularly, we investigated the presence of druggable binding sites on the CIN85 surface which provided new insights for the structure-based design of novel MUC1-CIN85 PPI inhibitors as anti-metastatic agents.

| S-EPMC7825788 | biostudies-literature

Spatiotemporal Imputation of MAIAC AOD Using Deep Learning with Downscaling.

Project description:Aerosols have adverse health effects and play a significant role in the climate as well. The Multiangle Implementation of Atmospheric Correction (MAIAC) provides Aerosol Optical Depth (AOD) at high temporal (daily) and spatial (1 km) resolution, making it particularly useful to infer and characterize spatiotemporal variability of aerosols at a fine spatial scale for exposure assessment and health studies. However, clouds and conditions of high surface reflectance result in a significant proportion of missing MAIAC AOD. To fill these gaps, we present an imputation approach using deep learning with downscaling. Using a baseline autoencoder, we leverage residual connections in deep neural networks to boost learning and parameter sharing to reduce overfitting, and conduct bagging to reduce error variance in the imputations. Downscaled through a similar auto-encoder based deep residual network, Modern-Era Retrospective analysis for Research and Applications Version 2 (MERRA-2) GMI Replay Simulation (M2GMI) data were introduced to the network as an important gap-filling feature that varies in space to be used for missingness imputations. Imputing weekly MAIAC AOD from 2000 to 2016 over California, a state with considerable geographic heterogeneity, our full (non-full) residual network achieved mean R2 = 0.94 (0.86) [RMSE = 0.007 (0.01)] in an independent test, showing considerably better performance than a regular neural network or non-linear generalized additive model (mean R2 = 0.78-0.81; mean RMSE = 0.013-0.015). The adjusted imputed as well as combined imputed and observed MAIAC AOD showed strong correlation with Aerosol Robotic Network (AERONET) AOD (R = 0.83; R2 = 0.69, RMSE = 0.04). Our results show that we can generate reliable imputations of missing AOD through a deep learning approach, having important downstream air quality modeling applications.

| S-EPMC7063693 | biostudies-literature

DNC4mC-Deep: Identification and Analysis of DNA N4-Methylcytosine Sites Based on Different Encoding Schemes By Using Deep Learning.

Project description:N4-methylcytosine as one kind of modification of DNA has a critical role which alters genetic performance such as protein interactions, conformation, stability in DNA as well as the regulation of gene expression same cell developmental and genomic imprinting. Some different 4mC site identifiers have been proposed for various species. Herein, we proposed a computational model, DNC4mC-Deep, including six encoding techniques plus a deep learning model to predict 4mC sites in the genome of F. vesca, R. chinensis, and Cross-species dataset. It was demonstrated by the 10-fold cross-validation test to get superior performance. The DNC4mC-Deep obtained 0.829 and 0.929 of MCC on F. vesca and R. chinensis training dataset, respectively, and 0.814 on cross-species. This means the proposed method outperforms the state-of-the-art predictors at least 0.284 and 0.265 on F. vesca and R. chinensis training dataset in turn. Furthermore, the DNC4mC-Deep achieved 0.635 and 0.565 of MCC on F. vesca and R. chinensis independent dataset, respectively, and 0.562 on cross-species which shows it can achieve the best performance to predict 4mC sites as compared to the state-of-the-art predictor.

| S-EPMC7465362 | biostudies-literature

Finding Druggable Sites in Proteins Using TACTICS.

Project description:Structure-based drug discovery efforts require knowledge of where drug-binding sites are located on target proteins. To address the challenge of finding druggable sites, we developed a machine-learning algorithm called TACTICS (trajectory-based analysis of conformations to identify cryptic sites), which uses an ensemble of molecular structures (such as molecular dynamics simulation data) as input. First, TACTICS uses k-means clustering to select a small number of conformations that represent the overall conformational heterogeneity of the data. Then, TACTICS uses a random forest model to identify potentially bindable residues in each selected conformation, based on protein motion and geometry. Lastly, residues in possible binding pockets are scored using fragment docking. As proof-of-principle, TACTICS was applied to the analysis of simulations of the SARS-CoV-2 main protease and methyltransferase and the Yersinia pestis aryl carrier protein. Our approach recapitulates known small-molecule binding sites and predicts the locations of sites not previously observed in experimentally determined structures. The TACTICS code is available at https://github.com/Albert-Lau-Lab/tactics_protein_analysis.

| S-EPMC8631419 | biostudies-literature

TS-m6A-DL: Tissue-specific identification of N6-methyladenosine sites using a universal deep learning model.

Project description:The most communal post-transcriptional modification, N6-methyladenosine (m6A), is associated with a number of crucial biological processes. The precise detection of m6A sites around the genome is critical for revealing its regulatory function and providing new insights into drug design. Although both experimental and computational models for detecting m6A sites have been introduced, but these conventional methods are laborious and expensive. Furthermore, only a handful of these models are capable of detecting m6A sites in various tissues. Therefore, a more generic and optimized computational method for detecting m6A sites in different tissues is required. In this paper, we proposed a universal model using a deep neural network (DNN) and named it TS-m6A-DL, which can classify m6A sites in several tissues of humans (Homo sapiens), mice (Mus musculus), and rats (Rattus norvegicus). To extract RNA sequence features and to convert the input into numerical format for the network, we utilized one-hot-encoding method. The model was tested using fivefold cross-validation and its stability was measured using independent datasets. The proposed model, TS-m6A-DL, achieved accuracies in the range of 75-85% using the fivefold cross-validation method and 72-84% on the independent datasets. Finally, to authenticate the generalization of the model, we performed cross-species testing and proved the generalization ability by achieving state-of-the-art results.

| S-EPMC8383060 | biostudies-literature

Deep learning identifies genome-wide DNA binding sites of long noncoding RNAs.

Project description:Long noncoding RNAs (lncRNAs) can exert their function by interacting with the DNA via triplex structure formation. Even though this has been validated with a handful of experiments, a genome-wide analysis of lncRNA-DNA binding is needed. In this paper, we develop and interpret deep learning models that predict the genome-wide binding sites deciphered by ChIRP-Seq experiments of 12 different lncRNAs. Among the several deep learning architectures tested, a simple architecture consisting of two convolutional neural network layers performed the best suggesting local sequence patterns as determinants of the interaction. Further interpretation of the kernels in the model revealed that these local sequence patterns form triplex structures with the corresponding lncRNAs. We uncovered several novel triplexes forming domains (TFDs) of these 12 lncRNAs and previously experimentally verified TFDs of lncRNAs HOTAIR and MEG3. We experimentally verified such two novel TFDs of lncRNAs HOTAIR and TUG1 predicted by our method (but previously unreported) using Electrophoretic mobility shift assays. In conclusion, we show that simple deep learning architecture can accurately predict genome-wide binding sites of lncRNAs and interpretation of the models suggest RNA:DNA:DNA triplex formation as a viable mechanism underlying lncRNA-DNA interactions at genome-wide level.

| S-EPMC6333433 | biostudies-literature

Characterization and Identification of Lysine Succinylation Sites based on Deep Learning Method.

Project description:Succinylation is a type of protein post-translational modification (PTM), which can play important roles in a variety of cellular processes. Due to an increasing number of site-specific succinylated peptides obtained from high-throughput mass spectrometry (MS), various tools have been developed for computationally identifying succinylated sites on proteins. However, most of these tools predict succinylation sites based on traditional machine learning methods. Hence, this work aimed to carry out the succinylation site prediction based on a deep learning model. The abundance of MS-verified succinylated peptides enabled the investigation of substrate site specificity of succinylation sites through sequence-based attributes, such as position-specific amino acid composition, the composition of k-spaced amino acid pairs (CKSAAP), and position-specific scoring matrix (PSSM). Additionally, the maximal dependence decomposition (MDD) was adopted to detect the substrate signatures of lysine succinylation sites by dividing all succinylated sequences into several groups with conserved substrate motifs. According to the results of ten-fold cross-validation, the deep learning model trained using PSSM and informative CKSAAP attributes can reach the best predictive performance and also perform better than traditional machine-learning methods. Moreover, an independent testing dataset that truly did not exist in the training dataset was used to compare the proposed method with six existing prediction tools. The testing dataset comprised of 218 positive and 2621 negative instances, and the proposed model could yield a promising performance with 84.40% sensitivity, 86.99% specificity, 86.79% accuracy, and an MCC value of 0.489. Finally, the proposed method has been implemented as a web-based prediction tool (CNN-SuccSite), which is now freely accessible at http://csb.cse.yzu.edu.tw/CNN-SuccSite/ .

| S-EPMC6838336 | biostudies-literature

DPI_CDF: druggable protein identifier using cascade deep forest.

Project description:BackgroundDrug targets in living beings perform pivotal roles in the discovery of potential drugs. Conventional wet-lab characterization of drug targets is although accurate but generally expensive, slow, and resource intensive. Therefore, computational methods are highly desirable as an alternative to expedite the large-scale identification of druggable proteins (DPs); however, the existing in silico predictor's performance is still not satisfactory.MethodsIn this study, we developed a novel deep learning-based model DPI_CDF for predicting DPs based on protein sequence only. DPI_CDF utilizes evolutionary-based (i.e., histograms of oriented gradients for position-specific scoring matrix), physiochemical-based (i.e., component protein sequence representation), and compositional-based (i.e., normalized qualitative characteristic) properties of protein sequence to generate features. Then a hierarchical deep forest model fuses these three encoding schemes to build the proposed model DPI_CDF.ResultsThe empirical outcomes on 10-fold cross-validation demonstrate that the proposed model achieved 99.13 % accuracy and 0.982 of Matthew's-correlation-coefficient (MCC) on the training dataset. The generalization power of the trained model is further examined on an independent dataset and achieved 95.01% of maximum accuracy and 0.900 MCC. When compared to current state-of-the-art methods, DPI_CDF improves in terms of accuracy by 4.27% and 4.31% on training and testing datasets, respectively. We believe, DPI_CDF will support the research community to identify druggable proteins and escalate the drug discovery process.AvailabilityThe benchmark datasets and source codes are available in GitHub: http://github.com/Muhammad-Arif-NUST/DPI_CDF .

| S-EPMC11334562 | biostudies-literature

Predicting TCR-Epitope Binding Specificity Using Deep Metric Learning and Multimodal Learning.

Project description:Understanding the recognition of specific epitopes by cytotoxic T cells is a central problem in immunology. Although predicting binding between peptides and the class I Major Histocompatibility Complex (MHC) has had success, predicting interactions between T cell receptors (TCRs) and MHC class I-peptide complexes (pMHC) remains elusive. This paper utilizes a convolutional neural network model employing deep metric learning and multimodal learning to perform two critical tasks in TCR-epitope binding prediction: identifying the TCRs that bind a given epitope from a TCR repertoire, and identifying the binding epitope of a given TCR from a list of candidate epitopes. Our model can perform both tasks simultaneously and reveals that inconsistent preprocessing of TCR sequences can confound binding prediction. Applying a neural network interpretation method identifies key amino acid sequence patterns and positions within the TCR, important for binding specificity. Contrary to common assumption, known crystal structures of TCR-pMHC complexes show that the predicted salient amino acid positions are not necessarily the closest to the epitopes, implying that physical proximity may not be a good proxy for importance in determining TCR-epitope specificity. Our work thus provides an insight into the learned predictive features of TCR-epitope binding specificity and advances the associated classification tasks.

| S-EPMC8071129 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data