Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

Research output: Contribution to journal › Review › peer-review

Standard

Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development. / Salo-Ahen, Outi M. H.; Alanko, Ida; Bhadane, Rajendra; Bonvin, Alexandre M. J. J.; Honorato, Rodrigo Vargas; Hossain, Shakhawath; Juffer, Andre H.; Kabedev, Aleksei; Lahtela-Kakkonen, Maija; Larsen, Anders Stottrup; Lescrinier, Eveline; Marimuthu, Parthiban; Mirza, Muhammad Usman; Mustafa, Ghulam; Nunes-Alves, Ariane; Pantsar, Tatu; Saadabadi, Atefeh; Singaravelu, Kalaimathy; Vanmeert, Michiel.

In: Processes, Vol. 9, No. 1, 71, 2021.

Research output: Contribution to journal › Review › peer-review

Harvard

Salo-Ahen, OMH, Alanko, I, Bhadane, R, Bonvin, AMJJ, Honorato, RV, Hossain, S, Juffer, AH, Kabedev, A, Lahtela-Kakkonen, M, Larsen, AS, Lescrinier, E, Marimuthu, P, Mirza, MU, Mustafa, G, Nunes-Alves, A, Pantsar, T, Saadabadi, A, Singaravelu, K & Vanmeert, M 2021, 'Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development', Processes, vol. 9, no. 1, 71. https://doi.org/10.3390/pr9010071

APA

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. (2021). Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development. Processes, 9(1), [71]. https://doi.org/10.3390/pr9010071

Vancouver

Salo-Ahen OMH, Alanko I, Bhadane R, Bonvin AMJJ, Honorato RV, Hossain S et al. Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development. Processes. 2021;9(1). 71. https://doi.org/10.3390/pr9010071

Author

Salo-Ahen, Outi M. H. ; Alanko, Ida ; Bhadane, Rajendra ; Bonvin, Alexandre M. J. J. ; Honorato, Rodrigo Vargas ; Hossain, Shakhawath ; Juffer, Andre H. ; Kabedev, Aleksei ; Lahtela-Kakkonen, Maija ; Larsen, Anders Stottrup ; Lescrinier, Eveline ; Marimuthu, Parthiban ; Mirza, Muhammad Usman ; Mustafa, Ghulam ; Nunes-Alves, Ariane ; Pantsar, Tatu ; Saadabadi, Atefeh ; Singaravelu, Kalaimathy ; Vanmeert, Michiel. / Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development. In: Processes. 2021 ; Vol. 9, No. 1.

Bibtex

@article{8e02852ee7dc4e688b6e34e72ab67af7,
title = "Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development",
abstract = "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.",
keywords = "binding free energy, computational pharmaceutics, computer-aided drug design, conformational ensemble, drug formulations, drug targets, enhanced sampling methods, ligand binding kinetics, protein flexibility, membrane interactions, COMPUTER-SIMULATIONS, INFORMATION-DRIVEN, MEMBRANE, PROTEINS, INSIGHTS",
author = "Salo-Ahen, {Outi M. H.} and Ida Alanko and Rajendra Bhadane and Bonvin, {Alexandre M. J. J.} and Honorato, {Rodrigo Vargas} and Shakhawath Hossain and Juffer, {Andre H.} and Aleksei Kabedev and Maija Lahtela-Kakkonen and Larsen, {Anders Stottrup} and Eveline Lescrinier and Parthiban Marimuthu and Mirza, {Muhammad Usman} and Ghulam Mustafa and Ariane Nunes-Alves and Tatu Pantsar and Atefeh Saadabadi and Kalaimathy Singaravelu and Michiel Vanmeert",
year = "2021",
doi = "10.3390/pr9010071",
language = "English",
volume = "9",
journal = "Processes",
issn = "2227-9717",
publisher = "MDPI AG",
number = "1",

}

RIS

TY - JOUR

T1 - Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

AU - Salo-Ahen, Outi M. H.

AU - Alanko, Ida

AU - Bhadane, Rajendra

AU - Bonvin, Alexandre M. J. J.

AU - Honorato, Rodrigo Vargas

AU - Hossain, Shakhawath

AU - Juffer, Andre H.

AU - Kabedev, Aleksei

AU - Lahtela-Kakkonen, Maija

AU - Larsen, Anders Stottrup

AU - Lescrinier, Eveline

AU - Marimuthu, Parthiban

AU - Mirza, Muhammad Usman

AU - Mustafa, Ghulam

AU - Nunes-Alves, Ariane

AU - Pantsar, Tatu

AU - Saadabadi, Atefeh

AU - Singaravelu, Kalaimathy

AU - Vanmeert, Michiel

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - binding free energy

KW - computational pharmaceutics

KW - computer-aided drug design

KW - conformational ensemble

KW - drug formulations

KW - drug targets

KW - enhanced sampling methods

KW - ligand binding kinetics

KW - protein flexibility

KW - membrane interactions

KW - COMPUTER-SIMULATIONS

KW - INFORMATION-DRIVEN

KW - MEMBRANE

KW - PROTEINS

KW - INSIGHTS

U2 - 10.3390/pr9010071

DO - 10.3390/pr9010071

M3 - Review

VL - 9

JO - Processes

JF - Processes

SN - 2227-9717

IS - 1

M1 - 71

ER -

ID: 257745272