Journal
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
Volume 18, Issue -, Pages 189-198Publisher
ELSEVIER
DOI: 10.1016/j.csbj.2019.12.004
Keywords
KRAS; Ras Proteins; Proto-Oncogene Proteins p21(ras); Cancer; Molecular Dynamics Simulation; Protein conformation; Drug discovery
Funding
- European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant [839230]
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One of the most common drivers in human cancer is the mutant KRAS protein. Not so long ago KRAS was considered as an undruggable oncoprotein. After a long struggle, however, we finally see some light at the end of the tunnel as promising KRAS targeted therapies are in or approaching clinical trials. In recent years, together with the promising progress in RAS drug discovery, our understanding of KRAS has increased tremendously. This progress has been accompanied with a resurgence of publicly available KRAS structures, which were limited to nine structures less than ten years ago. Furthermore, the ever-increasing computational capacity has made biologically relevant timescales accessible, enabling molecular dynamics (MD) simulations to study the dynamics of KRAS protein in more detail at the atomistic level. In this minireview, my aim is to provide the reader an overview of the publicly available KRAS structural data, insights to conformational dynamics revealed by experiments and what we have learned from MD simulations. Also, I will discuss limitations of the current data and provide suggestions for future research related to KRAS, which would fill out the existing gaps in our knowledge and provide guidance in deciphering this enigmatic oncoprotein. (C) 2019 The Author. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.
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