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GNINA 1.0: molecular docking with deep learning.

作者信息

McNutt Andrew T, Francoeur Paul, Aggarwal Rishal, Masuda Tomohide, Meli Rocco, Ragoza Matthew, Sunseri Jocelyn, Koes David Ryan

机构信息

Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, USA.

Center for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology, Hyderabad, 500 032, India.

出版信息

J Cheminform. 2021 Jun 9;13(1):43. doi: 10.1186/s13321-021-00522-2.


DOI:10.1186/s13321-021-00522-2
PMID:34108002
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8191141/
Abstract

Molecular docking computationally predicts the conformation of a small molecule when binding to a receptor. Scoring functions are a vital piece of any molecular docking pipeline as they determine the fitness of sampled poses. Here we describe and evaluate the 1.0 release of the Gnina docking software, which utilizes an ensemble of convolutional neural networks (CNNs) as a scoring function. We also explore an array of parameter values for Gnina 1.0 to optimize docking performance and computational cost. Docking performance, as evaluated by the percentage of targets where the top pose is better than 2Å root mean square deviation (Top1), is compared to AutoDock Vina scoring when utilizing explicitly defined binding pockets or whole protein docking. GNINA, utilizing a CNN scoring function to rescore the output poses, outperforms AutoDock Vina scoring on redocking and cross-docking tasks when the binding pocket is defined (Top1 increases from 58% to 73% and from 27% to 37%, respectively) and when the whole protein defines the binding pocket (Top1 increases from 31% to 38% and from 12% to 16%, respectively). The derived ensemble of CNNs generalizes to unseen proteins and ligands and produces scores that correlate well with the root mean square deviation to the known binding pose. We provide the 1.0 version of GNINA under an open source license for use as a molecular docking tool at https://github.com/gnina/gnina .

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/29a6f6c24f08/13321_2021_522_Fig13_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/ad4a363e9524/13321_2021_522_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/07a126ad6586/13321_2021_522_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/5180fb1094ea/13321_2021_522_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/70e006c285ba/13321_2021_522_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/24bdfbf38872/13321_2021_522_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/dacb43587244/13321_2021_522_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/803c4b05f45d/13321_2021_522_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/5aadb7019a40/13321_2021_522_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/03843c0d307e/13321_2021_522_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/8db09a0d32ee/13321_2021_522_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/c3857682ecab/13321_2021_522_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/86c7a07ed850/13321_2021_522_Fig12_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/29a6f6c24f08/13321_2021_522_Fig13_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/ad4a363e9524/13321_2021_522_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/07a126ad6586/13321_2021_522_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/5180fb1094ea/13321_2021_522_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/70e006c285ba/13321_2021_522_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/24bdfbf38872/13321_2021_522_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/dacb43587244/13321_2021_522_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/803c4b05f45d/13321_2021_522_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/5aadb7019a40/13321_2021_522_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/03843c0d307e/13321_2021_522_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/8db09a0d32ee/13321_2021_522_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/c3857682ecab/13321_2021_522_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/86c7a07ed850/13321_2021_522_Fig12_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/8191141/29a6f6c24f08/13321_2021_522_Fig13_HTML.jpg

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本文引用的文献

[1]
Generating 3D molecules conditional on receptor binding sites with deep generative models.

Chem Sci. 2022-2-7

[2]
Learning protein-ligand binding affinity with atomic environment vectors.

J Cheminform. 2021-8-14

[3]
Guiding Conventional Protein-Ligand Docking Software with Convolutional Neural Networks.

J Chem Inf Model. 2020-10-26

[4]
Three-Dimensional Convolutional Neural Networks and a Cross-Docked Data Set for Structure-Based Drug Design.

J Chem Inf Model. 2020-9-28

[5]
Autodock Vina Adopts More Accurate Binding Poses but Autodock4 Forms Better Binding Affinity.

J Chem Inf Model. 2020-1-27

[6]
MathDL: mathematical deep learning for D3R Grand Challenge 4.

J Comput Aided Mol Des. 2020-2

[7]
Cross-docking benchmark for automated pose and ranking prediction of ligand binding.

Protein Sci. 2019-11-28

[8]
Ultra-large library docking for discovering new chemotypes.

Nature. 2019-2-6

[9]
PotentialNet for Molecular Property Prediction.

ACS Cent Sci. 2018-11-28

[10]
Comparative Assessment of Scoring Functions: The CASF-2016 Update.

J Chem Inf Model. 2018-12-11

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