Top Med Chem (2021) 36: 25–42
https://doi.org/10.1007/7355_2020_106
© Springer Nature Switzerland AG 2020
Published online: 16 October 2020
Molecular Modeling of Protein Kinases:
Current Status and Challenges
Antti Poso
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
2 Virtual Screening and Docking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3 MD Simulations . . . . . . . . . .. . . . . . . . . . . . .. . . . . . . . . . . . . .. . . . . . . . . . . . .. . . . . . . . . . . . .. . . . . . . . . . . . . .. . 31
4 Allosteric Control of Kinases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
5 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
Abstract Molecular modeling and virtual screening are currently among the main
tools in kinase inhibitor design. In addition, molecular dynamics is actively used to
study structural features and function of kinases. During the last 20 years, computational power has dramatically increased, and at the same time, algorithms have
become more user-friendly. This has resulted in a situation where these powerful
methods are more easily available for even larger groups of scientists. To effectively
use computational methods, one should understand in great detail how protein
kinases are functioning and how current protein kinase inhibitors interact with the
kinase domain. This short review presents some of the main topics of kinase
modeling, concentrating especially on proper selection and preparation of protein
structure and general usage of MD simulations.
Keywords Docking, Molecular dynamics, Structure-based drug design, Virtual
screening
A. Poso (*)
School of Pharmacy, University of Eastern Finland, Kuopio, Finland
Department of Internal Medicine VIII, University Hospital Tübingen, Tübingen, Germany
e-mail: antti.poso@uef.fi
https://doi.org/10.1007/7355_2020_106
© Springer Nature Switzerland AG 2020
Published online: 16 October 2020
Molecular Modeling of Protein Kinases:
Current Status and Challenges
Antti Poso
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
2 Virtual Screening and Docking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3 MD Simulations . . . . . . . . . .. . . . . . . . . . . . .. . . . . . . . . . . . . .. . . . . . . . . . . . .. . . . . . . . . . . . .. . . . . . . . . . . . . .. . 31
4 Allosteric Control of Kinases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
5 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
Abstract Molecular modeling and virtual screening are currently among the main
tools in kinase inhibitor design. In addition, molecular dynamics is actively used to
study structural features and function of kinases. During the last 20 years, computational power has dramatically increased, and at the same time, algorithms have
become more user-friendly. This has resulted in a situation where these powerful
methods are more easily available for even larger groups of scientists. To effectively
use computational methods, one should understand in great detail how protein
kinases are functioning and how current protein kinase inhibitors interact with the
kinase domain. This short review presents some of the main topics of kinase
modeling, concentrating especially on proper selection and preparation of protein
structure and general usage of MD simulations.
Keywords Docking, Molecular dynamics, Structure-based drug design, Virtual
screening
A. Poso (*)
School of Pharmacy, University of Eastern Finland, Kuopio, Finland
Department of Internal Medicine VIII, University Hospital Tübingen, Tübingen, Germany
e-mail: antti.poso@uef.fi