Journal of Chemical Information and Modeling

, volume 60 , issue 12 , pages 5832-5852

Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19

Arbind Acharya ¹

Rupesh Agarwal ^{2, 3}

M. B. Baker ⁴

Jerome Baudry ⁵

Debsindhu Bhowmik ⁶

S. Boehm ⁴

K G Byler ⁵

S.Y. Chen ⁷

Leighton Coates ⁸

W Justin Cooper ^{2, 3}

O Demerdash ⁹

Isabella Daidone ¹⁰

J D Eblen ^{2, 11}

S. Ellingson ¹²

Stefano Forli ¹³

J. Glaser ¹⁴

James C. Gumbart ¹

J Gunnels ¹⁵

O. Hernandez ⁴

Stephan Irle ^{6, 16, 17}

D W Kneller ⁸

Andrey Kovalevsky ⁸

J. LARKIN ¹⁸

T. J. Lawrence ⁹

S. LEGRAND ¹⁸

Shanqin Liu ^{2, 11}

J C Mitchell ⁹

G. Park ⁷

J. M. Lakey ^{2, 3}

A. Pavlova ¹

Loukas Petridis ^{2, 11}

D. Poole ¹⁸

L Pouchard ⁷

A. Ramanathan ¹⁹

David F. Rogers ¹⁴

D Santos Martins ¹³

A Scheinberg ²⁰

A Sedova ⁹

Y. Shen ^{2, 3}

Jeremy M. Smith ^{2, 11}

Micholas Dean Smith ^{2, 11}

C Soto ⁷

A. Tsaris ¹⁴

M Thavappiragasam ⁹

A F Tillack ¹³

Josh V. Vermaas ¹⁴

V Q Vuong ^{6, 16, 17}

J. Yin ¹⁴

S. Yoo ⁷

M. Zahran ²¹

Laura Zanetti Polzi ²²

Hide authors affiliations Show authors affiliations: 22 affiliations

School of Physics, Georgia Institute of Technology, Atlanta, Georgia 30332, United States |

UT/ORNL Center for Molecular Biophysics, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830, United States |

Graduate School of Genome Science and Technology, University of Tennessee, Knoxville, Tennessee 37996, United States |

⁴

Computer Science and Mathematics Division, Oak Ridge National Lab, Oak Ridge, Tennessee 37830, United States |

⁵

The University of Alabama in Huntsville, Department of Biological Sciences. 301 Sparkman Drive, Huntsville, Alabama 35899, United States |

⁶

Computational Sciences and Engineering Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, United States |

⁷

Computational Science Initiative, Brookhaven National Laboratory, Upton, New York 11973, United States |

⁸

Neutron Scattering Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, United States |

⁹

Biosciences Division, Oak Ridge National Lab, Oak Ridge, Tennessee 37830, United States |

¹⁰

Department of Physical and Chemical Sciences, University of L’Aquila, I-67010 L’Aquila, Italy |

¹¹

The University of Tennessee, Knoxville. Department of Biochemistry & Cellular and Molecular Biology, 309 Ken and Blaire Mossman Bldg. 1311 Cumberland Avenue, Knoxville, Tennessee 37996, United States |

¹²

University of Kentucky, Division of Biomedical Informatics, College of Medicine, UK Medical Center MN 150, Lexington Kentucky 40536, United States |

¹³

Scripps Research, La Jolla, California 92037, United States |

¹⁴

National Center for Computational Sciences, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830, United States |

¹⁵

HPC Engineering, Amazon Web Services, Seattle, Washington 98121, United States |

¹⁶

Chemical Sciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, United States |

¹⁷

Bredesen Center for Interdisciplinary Research and Graduate Education, University of Tennessee, Knoxville, Tennessee 37996, United States |

¹⁸

NVIDIA Corporation, Santa Clara, California 95051, United States |

¹⁹

Data Science and Learning Division, Argonne National Lab, Lemont, Illinois 60439, United States |

²⁰

Jubilee Development, Cambridge Massachusetts 02139, United States |

²¹

Department of Biological Sciences, New York City College of Technology, The City University of New York (CUNY), Brooklyn, New York 11201, United States |

²²

CNR Institute of Nanoscience, I-41125 Modena, Italy |

Publication type: Journal Article

Publication date: 2020-12-16

American Chemical Society (ACS)

Journal of Chemical Information and Modeling

scimago Q1

wos Q1

SJR: 1.467

CiteScore: 9.8

Impact factor: 5.3

ISSN: 15499596, 1549960X

DOI: 10.1021/acs.jcim.0c01010

Copy DOI

PubMed ID: 33326239

General Chemistry

Computer Science Applications

General Chemical Engineering

Library and Information Sciences

Abstract

We present a supercomputer-driven pipeline for in silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. Ensemble docking makes use of MD results by docking compound databases into representative protein binding-site conformations, thus taking into account the dynamic properties of the binding sites. We also describe preliminary results obtained for 24 systems involving eight proteins of the proteome of SARS-CoV-2. The MD involves temperature replica exchange enhanced sampling, making use of massively parallel supercomputing to quickly sample the configurational space of protein drug targets. Using the Summit supercomputer at the Oak Ridge National Laboratory, more than 1 ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to 10 configurations of each of the 24 SARS-CoV-2 systems using AutoDock Vina. Comparison to experiment demonstrates remarkably high hit rates for the top scoring tranches of compounds identified by our ensemble approach. We also demonstrate that, using Autodock-GPU on Summit, it is possible to perform exhaustive docking of one billion compounds in under 24 h. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and artificial intelligence (AI) methods to cluster MD trajectories and rescore docking poses.

Found

1 citation

Osolodkin Dmitry

🥼 🤝

PhD in Chemistry

80 publications, 1 719 citations

h-index: 23

Sechenov First Moscow State Medical University

M.P. Chumakov Federal Scientific Center for Research and Development of Immunobiological Drugs of the Russian Academy of Sciences

1 citation

Moryachkov Roman

PhD in Physics and Mathematics

15 publications, 88 citations

h-index: 5

Federal Research Center "Krasnoyarsk Science Center" of the Siberian Branch of the Russian Academy of Sciences

Research interests

Synchrotron radiation

1 citation

Fomina Anastasiia

5 publications, 21 citations

h-index: 3

Lomonosov Moscow State University

M.P. Chumakov Federal Scientific Center for Research and Development of Immunobiological Drugs of the Russian Academy of Sciences

Research interests

Medicinal Chemistry

1 citation

Belenkaya Svetlana

PhD in Biological/biomedical sciences

39 publications, 266 citations

h-index: 9

State Research Center of Virology and Biotechnology VECTOR

N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of the Siberian Branch of the Russian Academy of Sciences

1 citation

Nesmeyanova Valentina

19 publications, 125 citations

h-index: 6

State Research Center of Virology and Biotechnology VECTOR

Research interests

Biotechnology

Genetic engineering

1 citation

Mohammed Wafaa

35 publications, 280 citations, 266 reviews

h-index: 10

Al-Furat Al-Awsat Technical University

1 citation

Falco Antonio

79 publications, 641 citations, 62 reviews

h-index: 13

CEU Cardinal Herrera University

Research interests

Computational mathematics

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162

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GOST Copy

Acharya A. et al. Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19 // Journal of Chemical Information and Modeling. 2020. Vol. 60. No. 12. pp. 5832-5852.

GOST all authors (up to 50) Copy

Acharya A. et al. Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19 // Journal of Chemical Information and Modeling. 2020. Vol. 60. No. 12. pp. 5832-5852.

RIS |

Cite this

RIS Copy

TY - JOUR

DO - 10.1021/acs.jcim.0c01010

UR - https://doi.org/10.1021/acs.jcim.0c01010

TI - Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19

T2 - Journal of Chemical Information and Modeling

AU - Acharya, Arbind

AU - Agarwal, Rupesh

AU - Baker, M. B.

AU - Baudry, Jerome

AU - Bhowmik, Debsindhu

AU - Boehm, S.

AU - Byler, K G

AU - Chen, S.Y.

AU - Coates, Leighton

AU - Cooper, W Justin

AU - Demerdash, O

AU - Daidone, Isabella

AU - Eblen, J D

AU - Ellingson, S.

AU - Forli, Stefano

AU - Glaser, J.

AU - Gumbart, James C.

AU - Gunnels, J

AU - Hernandez, O.

AU - Irle, Stephan

AU - Kneller, D W

AU - Kovalevsky, Andrey

AU - LARKIN, J.

AU - Lawrence, T. J.

AU - LEGRAND, S.

AU - Liu, Shanqin

AU - Mitchell, J C

AU - Park, G.

AU - Lakey, J. M.

AU - Pavlova, A.

AU - Petridis, Loukas

AU - Poole, D.

AU - Pouchard, L

AU - Ramanathan, A.

AU - Rogers, David F.

AU - Santos Martins, D

AU - Scheinberg, A

AU - Sedova, A

AU - Shen, Y.

AU - Smith, Jeremy M.

AU - Smith, Micholas Dean

AU - Soto, C

AU - Tsaris, A.

AU - Thavappiragasam, M

AU - Tillack, A F

AU - Vermaas, Josh V.

AU - Vuong, V Q

AU - Yin, J.

AU - Yoo, S.

AU - Zahran, M.

AU - Zanetti Polzi, Laura

PY - 2020

DA - 2020/12/16

PB - American Chemical Society (ACS)

SP - 5832-5852

IS - 12

VL - 60

PMID - 33326239

SN - 1549-9596

SN - 1549-960X

ER -

BibTex |

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BibTex (up to 50 authors) Copy

@article{2020_Acharya,

author = {Arbind Acharya and Rupesh Agarwal and M. B. Baker and Jerome Baudry and Debsindhu Bhowmik and S. Boehm and K G Byler and S.Y. Chen and Leighton Coates and W Justin Cooper and O Demerdash and Isabella Daidone and J D Eblen and S. Ellingson and Stefano Forli and J. Glaser and James C. Gumbart and J Gunnels and O. Hernandez and Stephan Irle and D W Kneller and Andrey Kovalevsky and J. LARKIN and T. J. Lawrence and S. LEGRAND and Shanqin Liu and J C Mitchell and G. Park and J. M. Lakey and A. Pavlova and Loukas Petridis and D. Poole and L Pouchard and A. Ramanathan and David F. Rogers and D Santos Martins and A Scheinberg and A Sedova and Y. Shen and Jeremy M. Smith and Micholas Dean Smith and C Soto and A. Tsaris and M Thavappiragasam and A F Tillack and Josh V. Vermaas and V Q Vuong and J. Yin and S. Yoo and M. Zahran and others},

title = {Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19},

journal = {Journal of Chemical Information and Modeling},

year = {2020},

volume = {60},

publisher = {American Chemical Society (ACS)},

month = {dec},

url = {https://doi.org/10.1021/acs.jcim.0c01010},

number = {12},

pages = {5832--5852},

doi = {10.1021/acs.jcim.0c01010}

}

MLA

Cite this

MLA Copy

Acharya, Arbind, et al. “Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.” Journal of Chemical Information and Modeling, vol. 60, no. 12, Dec. 2020, pp. 5832-5852. https://doi.org/10.1021/acs.jcim.0c01010.

Publisher

American Chemical Society (ACS)

Journal

Journal of Chemical Information and Modeling

scimago Q1

wos Q1

SJR

1.467

CiteScore

9.8

Impact factor

5.3

ISSN

15499596 (Print)

1549960X (Electronic)

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