RosENet: Improving Binding Affinity Prediction by Leveraging Molecular Mechanics Energies with an Ensemble of 3D Convolutional Neural Networks

AbstractConvolutional neural networks (CNN) have been shown to outperform conventional methods in DNA-protien binding specificity prediction. However, whether we can transfer this success to protien-peptide binding affinity prediction depends on appropriate design of the CNN architectue that calls for thorough understanding how to match the architecture to the problem. Here we propose DeepMHC, a deep convolutional neural network (CNN) based protein-peptide binding prediction algorithm for achieving better performance in MHC-I peptide binding affinity prediction than conventional algorithms. Our model takes only raw binding peptide sequences as input without needing any human-designed features and othe physichochemical or evolutionary information of the amino acids. Our CNN models are shown to be able to learn non-linear relationships among the amino acid positions of the peptides to achieve highly competitive performance on most of the IEDB benchmark datasets with a single model architecture and without using any consensus or composite ensemble classifier models. By systematically exploring the best CNN architecture, we identified critical design considerations in CNN architecture development for peptide-MHC binding prediction.

Download Full-text

KDEEP: Protein–Ligand Absolute Binding Affinity Prediction via 3D-Convolutional Neural Networks

Journal of Chemical Information and Modeling ◽

10.1021/acs.jcim.7b00650 ◽

2018 ◽

Vol 58 (2) ◽

pp. 287-296 ◽

Cited By ~ 160

Author(s):

José Jiménez ◽

Miha Škalič ◽

Gerard Martínez-Rosell ◽

Gianni De Fabritiis

Keyword(s):

Neural Networks ◽

Binding Affinity ◽

Convolutional Neural Networks ◽

Binding Affinity Prediction ◽

Affinity Prediction

Download Full-text

BgN-Score and BsN-Score: Bagging and boosting based ensemble neural networks scoring functions for accurate binding affinity prediction of protein-ligand complexes

BMC Bioinformatics ◽

10.1186/1471-2105-16-s4-s8 ◽

2015 ◽

Vol 16 (S4) ◽

Cited By ~ 24

Author(s):

Hossam M Ashtawy ◽

Nihar R Mahapatra

Keyword(s):

Neural Networks ◽

Binding Affinity ◽

Scoring Functions ◽

Binding Affinity Prediction ◽

Affinity Prediction ◽

Ensemble Neural Networks

Download Full-text

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

Bioinformatics ◽

10.1093/bioinformatics/btaa858 ◽

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.

Download Full-text

GRAM: A True Null Model for Relative Binding Affinity Predictions

10.26434/chemrxiv.9956474 ◽

2019 ◽

Author(s):

Guanglei Cui ◽

Alan P. Graves ◽

Eric S. Manas

Keyword(s):

Binding Affinity ◽

Performance Metrics ◽

Null Model ◽

Performance Measure ◽

Interval Estimate ◽

Empirical Observation ◽

Binding Affinity Prediction ◽

Affinity Prediction ◽

Relative Binding Affinity ◽

Relative Binding

Relative binding affinity prediction is a critical component in computer aided drug design. Significant amount of effort has been dedicated to developing rapid and reliable in silico methods. However, robust assessment of their performance is still a complicated issue, as it requires a performance measure applicable in the prospective setting and more importantly a true null model that defines the expected performance of random in an objective manner. Although many performance metrics, such as correlation coefficient (r2), mean unsigned error (MUE), and room mean square error (RMSE), are frequently used in the literature, a true and non-trivial null model has yet been identified. To address this problem, here we introduce an interval estimate as an additional measure, namely prediction interval (PI), which can be estimated from the error distribution of the predictions. The benefits of using the interval estimate are 1) it provides the uncertainty range in the predicted activities, which is important in prospective applications; 2) a true null model with well-defined PI can be established. We provide one such example termed Gaussian Random Affinity Model (GRAM), which is based on the empirical observation that the affinity change in a typical lead optimization effort has the tendency to distribute normally N (0, s). Having an analytically defined PI that only depends on the variation in the activities, GRAM should in principle allow us to compare the performance of relative binding affinity prediction methods in a standard way, ultimately critical to measuring the progress made in algorithm development.

Download Full-text

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

10.26434/chemrxiv.9866912 ◽

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

Introduction: 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. Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.

Download Full-text