Application of Machine Learning Techniques to Predict Binding Affinity for Drug Targets: A Study of Cyclin-Dependent Kinase 2

2020 ◽  
Vol 28 (2) ◽  
pp. 253-265 ◽  
Author(s):  
Gabriela Bitencourt-Ferreira ◽  
Amauri Duarte da Silva ◽  
Walter Filgueira de Azevedo
Keyword(s):  
Machine Learning ◽  
Binding Affinity ◽  
Predictive Performance ◽  
Supervised Machine Learning ◽  
Machine Learning Techniques ◽  
Scoring Functions ◽  
Cyclin Dependent Kinase ◽  
Learning Models ◽  
Learning Techniques ◽  
Machine Learning Models

Background: The elucidation of the structure of cyclin-dependent kinase 2 (CDK2) made it possible to develop targeted scoring functions for virtual screening aimed to identify new inhibitors for this enzyme. CDK2 is a protein target for the development of drugs intended to modulate cellcycle progression and control. Such drugs have potential anticancer activities. Objective: Our goal here is to review recent applications of machine learning methods to predict ligand- binding affinity for protein targets. To assess the predictive performance of classical scoring functions and targeted scoring functions, we focused our analysis on CDK2 structures. Methods: We have experimental structural data for hundreds of binary complexes of CDK2 with different ligands, many of them with inhibition constant information. We investigate here computational methods to calculate the binding affinity of CDK2 through classical scoring functions and machine- learning models. Results: Analysis of the predictive performance of classical scoring functions available in docking programs such as Molegro Virtual Docker, AutoDock4, and Autodock Vina indicated that these methods failed to predict binding affinity with significant correlation with experimental data. Targeted scoring functions developed through supervised machine learning techniques showed a significant correlation with experimental data. Conclusion: Here, we described the application of supervised machine learning techniques to generate a scoring function to predict binding affinity. Machine learning models showed superior predictive performance when compared with classical scoring functions. Analysis of the computational models obtained through machine learning could capture essential structural features responsible for binding affinity against CDK2.

Computational Prediction of Binding Affinity for CDK2-ligand Complexes. A Protein Target for Cancer Drug Discovery

2021 ◽  
Vol 28 ◽  
Author(s):  
Martina Veit-Acosta ◽  
Walter Filgueira de Azevedo Junior
Keyword(s):  
Machine Learning ◽  
Ligand Binding ◽  
Binding Affinity ◽  
Physical Modeling ◽  
Predictive Performance ◽  
Supervised Machine Learning ◽  
Machine Learning Techniques ◽  
Scoring Functions ◽  
Protein Target ◽  
Learning Techniques

Background: CDK2 participates in the control of eukaryotic cell-cycle progression. Due to the great interest in CDK2 for drug development and the relative easiness in crystallizing this enzyme, we have over 400 structural studies focused on this protein target. This structural data is the basis for the development of computational models to estimate CDK2-ligand binding affinity. Objective: This work focuses on the recent developments in the application of supervised machine learning modeling to develop scoring functions to predict the binding affinity of CDK2. Method: We employed the structures available at the protein data bank and the ligand information accessed from the BindingDB, Binding MOAD, and PDBbind to evaluate the predictive performance of machine learning techniques combined with physical modeling used to calculate binding affinity. We compared this hybrid methodology with classical scoring functions available in docking programs. Results: Our comparative analysis of previously published models indicated that a model created using a combination of a mass-spring system and cross-validated Elastic Net to predict the binding affinity of CDK2-inhibitor complexes outperformed classical scoring functions available in AutoDock4 and AutoDock Vina. Conclusion: All studies reviewed here suggest that targeted machine learning models are superior to classical scoring functions to calculate binding affinities. Specifically for CDK2, we see that the combination of physical modeling with supervised machine learning techniques exhibits improved predictive performance to calculate the protein-ligand binding affinity. These results find theoretical support in the application of the concept of scoring function space.

Supervised machine learning techniques to predict binding affinity. A study for cyclin-dependent kinase 2

2017 ◽  
Vol 494 (1-2) ◽  
pp. 305-310 ◽  
Author(s):  
Maurício Boff de Ávila ◽  
Mariana Morrone Xavier ◽  
Val Oliveira Pintro ◽  
Walter Filgueira de Azevedo
Keyword(s):  
Machine Learning ◽  
Binding Affinity ◽  
Supervised Machine Learning ◽  
Machine Learning Techniques ◽  
Cyclin Dependent Kinase ◽  
Learning Techniques

Machine Learning-Based Scoring Functions. Development and Applications with SAnDReS.

2020 ◽  
Vol 27 ◽  
Author(s):  
Gabriela Bitencourt-Ferreira ◽  
Camila Rizzotto ◽  
Walter Filgueira de Azevedo Junior
Keyword(s):  
Machine Learning ◽  
Binding Affinity ◽  
Drug Targets ◽  
Computational Models ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Predictive Performance ◽  
Machine Learning Techniques ◽  
Scoring Functions ◽  
Molegro Virtual Docker

Background: Analysis of atomic coordinates of protein-ligand complexes can provide three-dimensional data to generate computational models to evaluate binding affinity and thermodynamic state functions. Application of machine learning techniques can create models to assess protein-ligand potential energy and binding affinity. These methods show superior predictive performance when compared with classical scoring functions available in docking programs. Objective: Our purpose here is to review the development and application of the program SAnDReS. We describe the creation of machine learning models to assess the binding affinity of protein-ligand complexes. Method: SAnDReS implements machine learning methods available in the scikit-learn library. This program is available for download at https://github.com/azevedolab/sandres. SAnDReS uses crystallographic structures, binding, and thermodynamic data to create targeted scoring functions. Results: Recent applications of the program SAnDReS to drug targets such as Coagulation factor Xa, cyclin-dependent kinases, and HIV-1 protease were able to create targeted scoring functions to predict inhibition of these proteins. These targeted models outperform classical scoring functions. Conclusion: Here, we reviewed the development of machine learning scoring functions to predict binding affinity through the application of the program SAnDReS. Our studies show the superior predictive performance of the SAnDReS-developed models when compared with classical scoring functions available in the programs such as AutoDock4, Molegro Virtual Docker, and AutoDock Vina.

scholarly journals Cocrystal Prediction Using Machine Learning Models and Descriptors

2021 ◽  
Vol 11 (3) ◽  
pp. 1323
Author(s):  
Medard Edmund Mswahili ◽  
Min-Jeong Lee ◽  
Gati Lother Martin ◽  
Junghyun Kim ◽  
Paul Kim ◽  
...  
Keyword(s):  
Machine Learning ◽  
Academic Research ◽  
Pharmaceutical Research ◽  
Machine Learning Techniques ◽  
Learning Models ◽  
Pharmaceutical Ingredients ◽  
Learning Techniques ◽  
Comparable Performance ◽  
Selection Algorithms ◽  
Machine Learning Models

Cocrystals are of much interest in industrial application as well as academic research, and screening of suitable coformers for active pharmaceutical ingredients is the most crucial and challenging step in cocrystal development. Recently, machine learning techniques are attracting researchers in many fields including pharmaceutical research such as quantitative structure-activity/property relationship. In this paper, we develop machine learning models to predict cocrystal formation. We extract descriptor values from simplified molecular-input line-entry system (SMILES) of compounds and compare the machine learning models by experiments with our collected data of 1476 instances. As a result, we found that artificial neural network shows great potential as it has the best accuracy, sensitivity, and F1 score. We also found that the model achieved comparable performance with about half of the descriptors chosen by feature selection algorithms. We believe that this will contribute to faster and more accurate cocrystal development.

scholarly journals Applying Machine Learning Techniques to Predict the Properties of Energetic Materials

2018 ◽  
Author(s):  
Daniel Elton ◽  
Zois Boukouvalas ◽  
Mark S. Butrico ◽  
Mark D. Fuge ◽  
Peter W. Chung
Keyword(s):  
Machine Learning ◽  
Energetic Materials ◽  
Molecular Structures ◽  
Machine Learning Techniques ◽  
Small Data ◽  
Detonation Pressure ◽  
Learning Models ◽  
Data Set ◽  
Learning Techniques ◽  
Machine Learning Models

We present a proof of concept that machine learning techniques can be used to predict the properties of CNOHF energetic molecules from their molecular structures. We focus on a small but diverse dataset consisting of 109 molecular structures spread across ten compound classes. Up until now, candidate molecules for energetic materials have been screened using predictions from expensive quantum simulations and thermochemical codes. We present a comprehensive comparison of machine learning models and several molecular featurization methods - sum over bonds, custom descriptors, Coulomb matrices, bag of bonds, and fingerprints. The best featurization was sum over bonds (bond counting), and the best model was kernel ridge regression. Despite having a small data set, we obtain acceptable errors and Pearson correlations for the prediction of detonation pressure, detonation velocity, explosive energy, heat of formation, density, and other properties out of sample. By including another dataset with 309 additional molecules in our training we show how the error can be pushed lower, although the convergence with number of molecules is slow. Our work paves the way for future applications of machine learning in this domain, including automated lead generation and interpreting machine learning models to obtain novel chemical insights.

scholarly journals Heartbeat Abnormality Detection using Machine Learning Models and Rate Variability (HRV) Data

2018 ◽  
Author(s):  
Pratik Vyas ◽  
Diptangshu Pandit
Keyword(s):  
Machine Learning ◽  
Heart Rate ◽  
Machine Learning Techniques ◽  
Data Series ◽  
Abnormality Detection ◽  
Learning Models ◽  
Heart Rate Data ◽  
Learning Techniques ◽  
Minimal Data ◽  
Machine Learning Models

The use of machine learning techniques in predictive health care is on the rise with minimal data used for training machine-learning models to derive high accuracy predictions. In this paper, we propose such a system, which utilizes Heart Rate Variability (HRV) as features for training machine learning models. This paper further benchmarks the usefulness of HRV as features calculated from basic heart-rate data using a window shifting method. The benchmarking has been conducted using different machine-learning classifiers such as artificial neural network, decision tree, k-nearest neighbour and naive bays classifier. Empirical results using MIT-BIH Arrhythmia database shows that the proposed system can be used for highly efficient predictability of abnormality in heartbeat data series.

scholarly journals Application of machine learning tools in classifying pedestrian crash types: A case study

2020 ◽  
Vol 2 (2) ◽  
pp. 106-119
Author(s):  
Subasish Das ◽  
Minh Le ◽  
Boya Dai
Keyword(s):  
Machine Learning ◽  
Training Data ◽  
Machine Learning Techniques ◽  
Analysis Tool ◽  
Learning Tools ◽  
Learning Models ◽  
Learning Techniques ◽  
Crash Types ◽  
Textual Content ◽  
Machine Learning Models

Abstract Crash occurrence is a complex phenomenon, and crashes associated with pedestrians and bicyclists are even more complex. Furthermore, pedestrian- and bicyclist-involved crashes are typically not reported in detail in state or national crash databases. To address this issue, developers created the Pedestrian and Bicycle Crash Analysis Tool (PBCAT). However, it is labour-intensive to manually identify the types of pedestrian and bicycle crash from crash-narrative reports and to classify different crash attributes from the textual content of police reports. Therefore, there is a need for a supporting tool that can assist practitioners in using PBCAT more efficiently and accurately. The objective of this study is to develop a framework for applying machine-learning models to classify crash types from unstructured textual content. In this study, the research team collected pedestrian crash-typing data from two locations in Texas. The XGBoost model was found to be the best classifier. The high prediction power of the XGBoost classifiers indicates that this machine-learning technique was able to classify pedestrian crash types with the highest accuracy rate (up to 77% for training data and 72% for test data). The findings demonstrate that advanced machine-learning models can extract underlying patterns and trends of crash mechanisms. This provides the basis for applying machine-learning techniques in addressing the crash typing issues associated with non-motorist crashes.

scholarly journals 311 A brief overview, comparison and practical applications of machine learning models

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 44-45
Author(s):  
Dan Tulpan
Keyword(s):  
Machine Learning ◽  
Machine Learning Techniques ◽  
Learning Models ◽  
Training Opportunity ◽  
Practical Applications ◽  
Learning Techniques ◽  
Hands On ◽  
Practical Session ◽  
Applications Of Machine Learning ◽  
Machine Learning Models

Abstract This is a hands-on workshop offered as a pre-conference training opportunity for researchers interested in applying machine learning techniques to animal science datasets with the purpose of classifying, clustering, performing linear and non-linear regressions or selecting a subset of features relevant to further studies. The objective of this workshop is to provide the audience with a way to formulate a problem such that it will be solvable by machine learning techniques and apply an exploratory analysis of various machine learning on different datasets. The workshop is structured in a hands-on format and includes a brief overview of basic notions about machine learning, a description of relevant models and evaluation metrics followed by a practical session. The practical session requires each attendee to bring their own laptop and have already installed the Waikato Environment for Knowledge Analysis (Weka) workbench for machine learning available from https://www.cs.waikato.ac.nz/ml/weka/ and all freely available machine learning models. The Weka installation of freely available machine learning models can be achieved by using the Weka Package Manager available from the Tools menu in the main application. Detailed information will be provided 2 weeks before the beginning of the workshop (week of July 5, 2020) at the following URL:http://animalbiosciences.uoguelph.ca/~dtulpan/conferences/asas2020_mlworkshop/

scholarly journals Calibration of Machine Learning Models

2010 ◽  
pp. 128-146 ◽  
Author(s):  
Antonio Bella ◽  
Cèsar Ferri ◽  
José Hernández-Orallo ◽  
María José Ramírez-Quintana
Keyword(s):  
Machine Learning ◽  
Single Case ◽  
Machine Learning Techniques ◽  
Average Error ◽  
Learning Models ◽  
Classifier Calibration ◽  
Learning Techniques ◽  
Probabilistic Classifier ◽  
Calibration Techniques ◽  
Machine Learning Models

The evaluation of machine learning models is a crucial step before their application because it is essential to assess how well a model will behave for every single case. In many real applications, not only is it important to know the “total” or the “average” error of the model, it is also important to know how this error is distributed and how well confidence or probability estimations are made. Many current machine learning techniques are good in overall results but have a bad distribution assessment of the error. For these cases, calibration techniques have been developed as postprocessing techniques in order to improve the probability estimation or the error distribution of an existing model. This chapter presents the most common calibration techniques and calibration measures. Both classification and regression are covered, and a taxonomy of calibration techniques is established. Special attention is given to probabilistic classifier calibration.

scholarly journals Artificial Intelligence to Predict Mortality in Critically ill COVID-19 Patients Using Data from the First 24h: A Case Study from Lombardy Outbreak

2021 ◽  
Author(s):  
Massimiliano Greco ◽  
Giovanni Angelotti ◽  
Pier Francesco Caruso ◽  
Alberto Zanella ◽  
Niccolò Stomeo ◽  
...  
Keyword(s):  
Machine Learning ◽  
Predictive Performance ◽  
Supervised Machine Learning ◽  
Machine Learning Techniques ◽  
Chronic Obstructive ◽  
Complex Data ◽  
Icu Admission ◽  
Lower Performance ◽  
Learning Techniques ◽  
Using Data

Abstract Introduction: SARS-CoV-2 infection was first identified at the end of 2019 in China, and subsequently spread globally. COVID-19 disease frequently affects the lungs leading to bilateral viral pneumonia, progressing in some cases to severe respiratory failure requiring ICU admission and mechanical ventilation. Risk stratification at ICU admission is fundamental for resource allocation and decision making, considering that baseline comorbidities, age, and patient conditions at admission have been associated to poorer outcomes. Supervised machine learning techniques are increasingly diffuse in clinical medicine and can predict mortality and test associations reaching high predictive performance. We assessed performances of a machine learning approach to predict mortality in COVID-19 patients admitted to ICU using data from the Lombardy ICU Network.Methods: this is a secondary analysis of prospectively collected data from Lombardy ICU network. To predict survival at 7-,14- and 28 days we built two different models; model A included patient demographics, medications before admission and comorbidities, while model B also included the data of the first day since ICU admission. 10-fold cross validation was repeated 2500 times, to ensure optimal hyperparameter choice. The only constrain imposed to model optimization was the choice of logistic regression as final layer to increase clinical interpretability. Different imputation and over-sampling techniques were employed in model training.Results 1503 patients were included, with 766 deaths (51%). Exploratory analysis and Kaplan-Meier curves demonstrated mortality association with age and gender. Model A and B reached the greatest predictive performance at 28 days (AUC 0.77 and 0.79), with lower performance at 14 days (AUC 0.72 and 0.74) and 7 days (AUC 0.68 and 0.71). Male gender, age and number of comorbidities were strongly associated with mortality in both models. Among comorbidities, chronic kidney disease and chronic obstructive pulmonary disease demonstrated association. Mode of ventilatory assistance at ICU admission and Fraction of Inspired oxygen were associated with mortality in model B.Conclusions Supervised machine learning models demonstrated good performance in prediction of 28-day mortality. 7-days and 14-days predictions demonstrated lower performance. Machine learning techniques may be useful in emergency phases to reach higher predictive performance with reduced human supervision using complex data.

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