University of Oulu

Salo-Ahen, O.M.H.; Alanko, I.; Bhadane, R.; Bonvin, A.M.J.J.; Honorato, R.V.; Hossain, S.; Juffer, A.H.; Kabedev, A.; Lahtela-Kakkonen, M.; Larsen, A.S.; Lescrinier, E.; Marimuthu, P.; Mirza, M.U.; Mustafa, G.; Nunes-Alves, A.; Pantsar, T.; Saadabadi, A.; Singaravelu, K.; Vanmeert, M. Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development. Processes 2021, 9, 71.

Molecular dynamics simulations in drug discovery and pharmaceutical development

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Author: Salo-Ahen, Outi M. H.1,2; Alanko, Ida1,2; Bhadane, Rajendra1,2;
Organizations: 1Pharmaceutical Sciences Laboratory (Pharmacy), Åbo Akademi University, Tykistökatu 6 A, Biocity, FI-20520 Turku, Finland
2Structural Bioinformatics Laboratory (Biochemistry), Åbo Akademi University, Tykistökatu 6 A, Biocity, FI-20520 Turku, Finland
3Faculty of Science-Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, 3584 CH Utrecht, The Netherlands
4Swedish Drug Delivery Forum (SDDF), Department of Pharmacy, Uppsala Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden
5Biocenter Oulu & Faculty of Biochemistry and Molecular Medicine, University of Oulu, Aapistie 7 A, FI-90014 Oulu, Finland
6School of Pharmacy, University of Eastern Finland, FI-70210 Kuopio, Finland
7Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 København Ø, Denmark
8Department of Pharmaceutical and Pharmacological Sciences, Rega Institute for Medical Research, Medicinal Chemistry, University of Leuven, B-3000 Leuven, Belgium
9Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
10Heidelberg Institute for Theoretical Studies (HITS), Schloß-Wolfsbrunnenweg 35, 69118 Heidelberg, Germany
11Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Im Neuenheimer Feld 282, 69120 Heidelberg, Germany
12Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmaceutical Sciences, Eberhard Karls University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany
13Turku Computer Science and Informatics, Department of Future Technologies, University of Turku, FI-20520 Turku, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 4.6 MB)
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Language: English
Published: Multidisciplinary Digital Publishing Institute, 2021
Publish Date: 2021-03-30


Molecular dynamics (MD) simulations have become increasingly useful in the modern drug development process. In this review, we give a broad overview of the current application possibilities of MD in drug discovery and pharmaceutical development. Starting from the target validation step of the drug development process, we give several examples of how MD studies can give important insights into the dynamics and function of identified drug targets such as sirtuins, RAS proteins, or intrinsically disordered proteins. The role of MD in antibody design is also reviewed. In the lead discovery and lead optimization phases, MD facilitates the evaluation of the binding energetics and kinetics of the ligand-receptor interactions, therefore guiding the choice of the best candidate molecules for further development. The importance of considering the biological lipid bilayer environment in the MD simulations of membrane proteins is also discussed, using G-protein coupled receptors and ion channels as well as the drug-metabolizing cytochrome P450 enzymes as relevant examples. Lastly, we discuss the emerging role of MD simulations in facilitating the pharmaceutical formulation development of drugs and candidate drugs. Specifically, we look at how MD can be used in studying the crystalline and amorphous solids, the stability of amorphous drug or drug-polymer formulations, and drug solubility. Moreover, since nanoparticle drug formulations are of great interest in the field of drug delivery research, different applications of nano-particle simulations are also briefly summarized using multiple recent studies as examples. In the future, the role of MD simulations in facilitating the drug development process is likely to grow substantially with the increasing computer power and advancements in the development of force fields and enhanced MD methodologies.

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Series: Processes
ISSN: 2227-9717
ISSN-E: 2227-9717
ISSN-L: 2227-9717
Volume: 9
Issue: 1
Article number: 71
DOI: 10.3390/pr9010071
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3111 Biomedicine
Funding: This work was supported by the BioExcel CoE (, a project funded by the European Horizon 2020 program under grant agreements 675728 and 823830 (R.V.H.); the Åbo Akademi University research mobility program in the research profiling area of Drug Development and Diagnostics (R.B.); Åbo Akademi University research grant (A.S.); Tor, Joe and Pentti Borg’s Foundation in 2020 (P.M.); the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes, process number 88881.162167/2017-01), the Alexander von Humboldt Foundation, and the Klaus Tschira Foundation (A.N.A.); the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 839230 and Orion Research Foundation sr. (T.P.); Vinnova (Dnr 2017-02690), the European Research Council Grant 638965 (A.K. and S.H.) and the Academy of Finland grant number 315824 (M.L.-K.).
Copyright information: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (