MDeePred: novel multi-channel protein featurization for deep learning-based binding affinity prediction in drug discovery

2020 ◽  
Author(s):  
A S Rifaioglu ◽  
R Cetin Atalay ◽  
D Cansen Kahraman ◽  
T Doğan ◽  
M Martin ◽  
...  
Keyword(s):  
Neural Networks ◽  
Deep Learning ◽  
Drug Discovery ◽  
Binding Affinity ◽  
Deep Neural Networks ◽  
State Of The Art ◽  
Target Protein ◽  
Binding Affinity Prediction ◽  
Affinity Prediction ◽  
Compound Target

Abstract Motivation Identification of interactions between bioactive small molecules and target proteins is crucial for novel drug discovery, drug repurposing and uncovering off-target effects. Due to the tremendous size of the chemical space, experimental bioactivity screening efforts require the aid of computational approaches. Although deep learning models have been successful in predicting bioactive compounds, effective and comprehensive featurization of proteins, to be given as input to deep neural networks, remains a challenge. Results Here, we present a novel protein featurization approach to be used in deep learning-based compound–target protein binding affinity prediction. In the proposed method, multiple types of protein features such as sequence, structural, evolutionary and physicochemical properties are incorporated within multiple 2D vectors, which is then fed to state-of-the-art pairwise input hybrid deep neural networks to predict the real-valued compound–target protein interactions. The method adopts the proteochemometric approach, where both the compound and target protein features are used at the input level to model their interaction. The whole system is called MDeePred and it is a new method to be used for the purposes of computational drug discovery and repositioning. We evaluated MDeePred on well-known benchmark datasets and compared its performance with the state-of-the-art methods. We also performed in vitro comparative analysis of MDeePred predictions with selected kinase inhibitors’ action on cancer cells. MDeePred is a scalable method with sufficiently high predictive performance. The featurization approach proposed here can also be utilized for other protein-related predictive tasks. Availability and implementation The source code, datasets, additional information and user instructions of MDeePred are available at https://github.com/cansyl/MDeePred. Supplementary information Supplementary data are available at Bioinformatics online.

Improving the Accuracy of Protein-Ligand Binding Affinity Prediction by Deep Learning Models: Benchmark and Model

2019 ◽  
Author(s):  
Mohammad Rezaei ◽  
Yanjun Li ◽  
Xiaolin Li ◽  
Chenglong Li
Keyword(s):  
Deep Learning ◽  
Drug Design ◽  
Binding Affinity ◽  
Benchmark Dataset ◽  
Rational Drug Design ◽  
Learning Models ◽  
Structure Based Drug Design ◽  
Binding Affinity Prediction ◽  
Affinity Prediction ◽  
Rational Drug

<b>Introduction:</b> The ability to discriminate among ligands binding to the same protein target in terms of their relative binding affinity lies at the heart of structure-based drug design. Any improvement in the accuracy and reliability of binding affinity prediction methods decreases the discrepancy between experimental and computational results.<br><b>Objectives:</b> The primary objectives were to find the most relevant features affecting binding affinity prediction, least use of manual feature engineering, and improving the reliability of binding affinity prediction using efficient deep learning models by tuning the model hyperparameters.<br><b>Methods:</b> The binding site of target proteins was represented as a grid box around their bound ligand. Both binary and distance-dependent occupancies were examined for how an atom affects its neighbor voxels in this grid. A combination of different features including ANOLEA, ligand elements, and Arpeggio atom types were used to represent the input. An efficient convolutional neural network (CNN) architecture, DeepAtom, was developed, trained and tested on the PDBbind v2016 dataset. Additionally an extended benchmark dataset was compiled to train and evaluate the models.<br><b>Results: </b>The best DeepAtom model showed an improved accuracy in the binding affinity prediction on PDBbind core subset (Pearson’s R=0.83) and is better than the recent state-of-the-art models in this field. In addition when the DeepAtom model was trained on our proposed benchmark dataset, it yields higher correlation compared to the baseline which confirms the value of our model.<br><b>Conclusions:</b> The promising results for the predicted binding affinities is expected to pave the way for embedding deep learning models in virtual screening and rational drug design fields.

scholarly journals Representing Deep Neural Networks Latent Space Geometries with Graphs

Algorithms ◽  
2021 ◽  
Vol 14 (2) ◽  
pp. 39
Author(s):  
Carlos Lassance ◽  
Vincent Gripon ◽  
Antonio Ortega
Keyword(s):  
Machine Learning ◽  
Neural Networks ◽  
Deep Learning ◽  
Objective Function ◽  
Learning Process ◽  
Deep Neural Networks ◽  
State Of The Art ◽  
The Core ◽  
Learning Tasks ◽  
Latent Space

Deep Learning (DL) has attracted a lot of attention for its ability to reach state-of-the-art performance in many machine learning tasks. The core principle of DL methods consists of training composite architectures in an end-to-end fashion, where inputs are associated with outputs trained to optimize an objective function. Because of their compositional nature, DL architectures naturally exhibit several intermediate representations of the inputs, which belong to so-called latent spaces. When treated individually, these intermediate representations are most of the time unconstrained during the learning process, as it is unclear which properties should be favored. However, when processing a batch of inputs concurrently, the corresponding set of intermediate representations exhibit relations (what we call a geometry) on which desired properties can be sought. In this work, we show that it is possible to introduce constraints on these latent geometries to address various problems. In more detail, we propose to represent geometries by constructing similarity graphs from the intermediate representations obtained when processing a batch of inputs. By constraining these Latent Geometry Graphs (LGGs), we address the three following problems: (i) reproducing the behavior of a teacher architecture is achieved by mimicking its geometry, (ii) designing efficient embeddings for classification is achieved by targeting specific geometries, and (iii) robustness to deviations on inputs is achieved via enforcing smooth variation of geometry between consecutive latent spaces. Using standard vision benchmarks, we demonstrate the ability of the proposed geometry-based methods in solving the considered problems.

scholarly journals Development and evaluation of a deep learning model for protein–ligand binding affinity prediction

2018 ◽  
Vol 34 (21) ◽  
pp. 3666-3674 ◽  
Author(s):  
Marta M Stepniewska-Dziubinska ◽  
Piotr Zielenkiewicz ◽  
Pawel Siedlecki
Keyword(s):  
Deep Learning ◽  
Ligand Binding ◽  
Binding Affinity ◽  
Learning Model ◽  
Binding Affinity Prediction ◽  
Affinity Prediction ◽  
Deep Learning Model

scholarly journals ISLAND: in-silico proteins binding affinity prediction using sequence information

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Wajid Arshad Abbasi ◽  
Adiba Yaseen ◽  
Fahad Ul Hassan ◽  
Saiqa Andleeb ◽  
Fayyaz Ul Amir Afsar Minhas
Keyword(s):  
Machine Learning ◽  
Protein Binding ◽  
Binding Affinity ◽  
State Of The Art ◽  
Protein Complexes ◽  
Protein Structures ◽  
Sequence Information ◽  
Binding Affinity Prediction ◽  
Generalization Performance ◽  
Affinity Prediction

Abstract Background Determining binding affinity in protein-protein interactions is important in the discovery and design of novel therapeutics and mutagenesis studies. Determination of binding affinity of proteins in the formation of protein complexes requires sophisticated, expensive and time-consuming experimentation which can be replaced with computational methods. Most computational prediction techniques require protein structures that limit their applicability to protein complexes with known structures. In this work, we explore sequence-based protein binding affinity prediction using machine learning. Method We have used protein sequence information instead of protein structures along with machine learning techniques to accurately predict the protein binding affinity. Results We present our findings that the true generalization performance of even the state-of-the-art sequence-only predictor is far from satisfactory and that the development of machine learning methods for binding affinity prediction with improved generalization performance is still an open problem. We have also proposed a sequence-based novel protein binding affinity predictor called ISLAND which gives better accuracy than existing methods over the same validation set as well as on external independent test dataset. A cloud-based webserver implementation of ISLAND and its python code are available at https://sites.google.com/view/wajidarshad/software. Conclusion This paper highlights the fact that the true generalization performance of even the state-of-the-art sequence-only predictor of binding affinity is far from satisfactory and that the development of effective and practical methods in this domain is still an open problem.

scholarly journals Mathematical deep learning for pose and binding affinity prediction and ranking in D3R Grand Challenges

2018 ◽  
Vol 33 (1) ◽  
pp. 71-82 ◽  
Author(s):  
Duc Duy Nguyen ◽  
Zixuan Cang ◽  
Kedi Wu ◽  
Menglun Wang ◽  
Yin Cao ◽  
...  
Keyword(s):  
Deep Learning ◽  
Binding Affinity ◽  
Binding Affinity Prediction ◽  
Affinity Prediction ◽  
Grand Challenges

scholarly journals DeepFrag: A Deep Convolutional Neural Network for Fragment-based Lead Optimization

2021 ◽  
Author(s):  
Harrison Green ◽  
David Ryan Koes ◽  
Jacob D Durrant
Keyword(s):  
Neural Network ◽  
Machine Learning ◽  
Drug Discovery ◽  
Virtual Screening ◽  
Convolutional Neural Network ◽  
Binding Affinity ◽  
Lead Optimization ◽  
Binding Affinity Prediction ◽  
Affinity Prediction ◽  
Computer Aided

Machine learning has been increasingly applied to the field of computer-aided drug discovery in recent years, leading to notable advances in binding-affinity prediction, virtual screening, and QSAR. Surprisingly, it is...

scholarly journals Binding affinity prediction for protein–ligand complex using deep attention mechanism based on intermolecular interactions

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sangmin Seo ◽  
Jonghwan Choi ◽  
Sanghyun Park ◽  
Jaegyoon Ahn
Keyword(s):  
Deep Learning ◽  
Binding Affinity ◽  
Prediction Models ◽  
Attention Mechanism ◽  
Scoring Functions ◽  
Ligand Complex ◽  
Structure Based Drug Design ◽  
Binding Affinity Prediction ◽  
Affinity Prediction ◽  
Proposed Model

Abstract Background Accurate prediction of protein–ligand binding affinity is important for lowering the overall cost of drug discovery in structure-based drug design. For accurate predictions, many classical scoring functions and machine learning-based methods have been developed. However, these techniques tend to have limitations, mainly resulting from a lack of sufficient energy terms to describe the complex interactions between proteins and ligands. Recent deep-learning techniques can potentially solve this problem. However, the search for more efficient and appropriate deep-learning architectures and methods to represent protein–ligand complex is ongoing. Results In this study, we proposed a deep-neural network model to improve the prediction accuracy of protein–ligand complex binding affinity. The proposed model has two important features, descriptor embeddings with information on the local structures of a protein–ligand complex and an attention mechanism to highlight important descriptors for binding affinity prediction. The proposed model performed better than existing binding affinity prediction models on most benchmark datasets. Conclusions We confirmed that an attention mechanism can capture the binding sites in a protein–ligand complex to improve prediction performance. Our code is available at https://github.com/Blue1993/BAPA.

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