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P-SaMI: a data-flow pattern to perform massively-parallel molecular docking experiments using a fully-flexible receptor model

Authors:

Patricia Hübler,

Duncan Ruiz,

João Eduardo Ferreira,

Osmar Norberto de SouzaAuthors Info & Claims

SAC '15: Proceedings of the 30th Annual ACM Symposium on Applied Computing

Pages 54 - 57

https://doi.org/10.1145/2695664.2695962

Published: 13 April 2015 Publication History

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Abstract

Molecular docking (MD) simulation is one of the four steps of the rational drug design. By the use of a fully-flexible receptor (FFR) model, protein flexibility can be explicitly considered during the drug design process. FFR models are composed of hundreds to several thousands of conformations to simulate the receptor flexibility in cell environments. So, for each conformation in the FFR model a MD simulation is executed and analyzed against a small molecule. However, it presents an important challenge due to small molecules databases, e.g. ZINC, have more than 21 million compounds available. It is computationally very demanding task to perform virtual screening of millions of ligands using an FFR model in a sequential mode.

This paper introduces a data-flow pattern to perform massively-parallel MD simulations using FFR models, named Self-adaptive Multiple Instances (P-SaMI). Based on a previously-clustered FFR model, P-SaMI permits to selectively perform experiments by the use of the Free Energy of Binding (FEB) output, used as quality criterion: smaller FEBs mean better results. The main goal achieved on using P-SaMI was the significant reduction of the number of docking experiments comparing with exhaustive ones, for a specific small molecule.

References

[1]

Kuntz, I. D. Structure-based Strategies for Drug Design and Discovery. Science. 257:1078--1082. 1992.

Crossref

Google Scholar

[2]

Goodsell, D. S., Olson, A. J. Automated docking of substrates to proteins by simulated annealing. Proteins. 8:195--202. 1990.

Crossref

Google Scholar

[3]

Morris, G. M.; Goodsell, D. S.; Halliday, R. S.; Huey, R.; Hart, W. E.; Belew, R. K.; Olson, A. J. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem. 19(14):1639-1662. 1998.

Crossref

Google Scholar

[4]

Carlson, H. A. Protein flexibility is an important component of structure-based drug discovery. Curr. Pharm. Des. 8:1571--1578. 2002.

Crossref

Google Scholar

[5]

van Gunsteren, W. F., Berendsen, H. J. C. Computer Simulation of Molecular Dynamics Methodology, Applications and Perspectives in Chemistry. Angew. Chem. Int. Ed. Engl. 29:992-1023. 1990.

Crossref

Google Scholar

[6]

Machado, K. S.; Winck, A. T.; Ruiz, D. D.; Norberto de Souza, O. Mining flexible-receptor molecular docking data. Wiley Interdisciplinary Reviews: Data Mining and Knowledge Discovery, 1:532-541. 2011.

Crossref

Google Scholar

[7]

LIN, J-H, Perryman, A. L., Schames, J. R., McCammon, J. A. Computational drug design accommodating receptor flexibility: the relaxed complex scheme. J. Am. Chem. Soc. 124:5632-5633. 2002.

Crossref

Google Scholar

[8]

Dessen, A.; Quémard, A.; Blanchard, J. S.; Jacobs, W. R.; JR Sacchettini, J. C. Crystal structure and function of the isoniazid target of Mycobacterium tuberculosis. Science, 267(5204):1638-1641. 1995.

Crossref

Google Scholar

[9]

Machado, K. Efficient Selection of Flexible Receptor Snapshots applied in Molecular Docking Simulations. PhD Thesis, in Portuguese. PUCRS-PPGCC; 2011.

Google Scholar

[10]

De Paris, R.; Frantz, F.; Norberto de Souza, O.: Ruiz, D. D. A. wFReDoW: A Cloud-Based Web Environment to Handle Molecular Docking Simulations of a Fully Flexible Receptor Model. BioMed Research International, 2013:1-12. 2013.

Crossref

Google Scholar

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De Paris RVahl Quevedo CRuiz DGargano Fde Souza O(2018)A selective method for optimizing ensemble docking-based experiments on an InhA Fully-Flexible receptor modelBMC Bioinformatics10.1186/s12859-018-2222-219:1Online publication date: 22-Jun-2018
https://doi.org/10.1186/s12859-018-2222-2
Paris RRuiz DSouza O(2015)A Cloud-Based Workflow Approach for Optimizing Molecular Docking Simulations of Fully-Flexible Receptor Models and Multiple LigandsProceedings of the 2015 IEEE 7th International Conference on Cloud Computing Technology and Science (CloudCom)10.1109/CloudCom.2015.43(495-498)Online publication date: 30-Nov-2015
https://dl.acm.org/doi/10.1109/CloudCom.2015.43

Index Terms

P-SaMI: a data-flow pattern to perform massively-parallel molecular docking experiments using a fully-flexible receptor model

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Published In

SAC '15: Proceedings of the 30th Annual ACM Symposium on Applied Computing

April 2015

2418 pages

ISBN:9781450331968

DOI:10.1145/2695664

Conference Chairs:
Roger L. Wainwright
University of Tulsa
,
Juan Manuel Corchado
University of Salamanca, Spain
,
Program Chairs:
Alessio Bechini
University of Pisa, Italy
,
Jiman Hong
Soongsil University, South Korea

Permission to make digital or hard copies of all or part of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for profit or commercial advantage and that copies bear this notice and the full citation on the first page. Copyrights for components of this work owned by others than ACM must be honored. Abstracting with credit is permitted. To copy otherwise, or republish, to post on servers or to redistribute to lists, requires prior specific permission and/or a fee. Request permissions from [email protected]

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Published: 13 April 2015

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SAC 2015: Symposium on Applied Computing

April 13 - 17, 2015

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SAC '15 Paper Acceptance Rate 291 of 1,211 submissions, 24%;

Overall Acceptance Rate 1,650 of 6,669 submissions, 25%

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De Paris RVahl Quevedo CRuiz DGargano Fde Souza O(2018)A selective method for optimizing ensemble docking-based experiments on an InhA Fully-Flexible receptor modelBMC Bioinformatics10.1186/s12859-018-2222-219:1Online publication date: 22-Jun-2018
https://doi.org/10.1186/s12859-018-2222-2
Paris RRuiz DSouza O(2015)A Cloud-Based Workflow Approach for Optimizing Molecular Docking Simulations of Fully-Flexible Receptor Models and Multiple LigandsProceedings of the 2015 IEEE 7th International Conference on Cloud Computing Technology and Science (CloudCom)10.1109/CloudCom.2015.43(495-498)Online publication date: 30-Nov-2015
https://dl.acm.org/doi/10.1109/CloudCom.2015.43

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Identification of potential ATP-competitive cyclin-dependent kinase 1 inhibitors: De novo drug generation, molecular docking, and molecular dynamics simulation

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In-vitro evaluation and in-silico studies applied on newly synthesized amide derivatives of N-phthaloylglycine as Butyrylcholinesterase (BChE) inhibitors

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