Lessons from computer simulations of Ras proteins in solution and in membrane

A great deal has been learned over the last several decades about the function of Ras proteins in solution and membrane environments. While much of this knowledge has been derived from a plethora of experimental techniques, computer simulations have also played a substantial role. Our goal here is t...

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Published inBiochimica et biophysica acta Vol. 1830; no. 11; pp. 5211 - 5218
Main Authors Prakash, Priyanka, Gorfe, Alemayehu A.
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 01.11.2013
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Abstract A great deal has been learned over the last several decades about the function of Ras proteins in solution and membrane environments. While much of this knowledge has been derived from a plethora of experimental techniques, computer simulations have also played a substantial role. Our goal here is to summarize the contribution of molecular simulations to our current understanding of normal and aberrant Ras function. We focus on lessons from molecular dynamics simulations in aqueous and membrane environments. The central message is that a close interaction between theory and simulation on the one hand and cell-biological, spectroscopic and other experimental approaches on the other has played, and will likely continue to play, a vital role in Ras research. Atomistic insights emerging from detailed simulations of Ras in solution and in bilayers may be the key to unlock the secret that to date prevented development of selective anti-Ras inhibitors for cancer therapy. •Contribution of molecular simulations to the study of Ras GTPases•Multi-scale molecular dynamics simulations of Ras in solution and in membrane•Dynamics plays an important role in the biological activity of Ras proteins.•Implications of simulations and protein motion for anti-cancer Ras inhibitors
AbstractList A great deal has been learned over the last several decades about the function of Ras proteins in solution and membrane environments. While much of this knowledge has been derived from a plethora of experimental techniques, computer simulations have also played a substantial role. Our goal here is to summarize the contribution of molecular simulations to our current understanding of normal and aberrant Ras function. We focus on lessons from molecular dynamics simulations in aqueous and membrane environments. The central message is that a close interaction between theory and simulation on the one hand and cell-biological, spectroscopic and other experimental approaches on the other has played, and will likely continue to play, a vital role in Ras research. Atomistic insights emerging from detailed simulations of Ras in solution and in bilayers may be the key to unlock the secret that to date prevented development of selective anti-Ras inhibitors for cancer therapy.
A great deal has been learned over the last several decades about the function of Ras proteins in solution and membrane environments. While much of this knowledge has been derived from a plethora of experimental techniques, computer simulations have also played a substantial role.BACKGROUNDA great deal has been learned over the last several decades about the function of Ras proteins in solution and membrane environments. While much of this knowledge has been derived from a plethora of experimental techniques, computer simulations have also played a substantial role.Our goal here is to summarize the contribution of molecular simulations to our current understanding of normal and aberrant Ras function. We focus on lessons from molecular dynamics simulations in aqueous and membrane environments.SCOPE OF REVIEWOur goal here is to summarize the contribution of molecular simulations to our current understanding of normal and aberrant Ras function. We focus on lessons from molecular dynamics simulations in aqueous and membrane environments.The central message is that a close interaction between theory and simulation on the one hand and cell-biological, spectroscopic and other experimental approaches on the other has played, and will likely continue to play, a vital role in Ras research.MAJOR CONCLUSIONSThe central message is that a close interaction between theory and simulation on the one hand and cell-biological, spectroscopic and other experimental approaches on the other has played, and will likely continue to play, a vital role in Ras research.Atomistic insights emerging from detailed simulations of Ras in solution and in bilayers may be the key to unlock the secret that to date prevented development of selective anti-Ras inhibitors for cancer therapy.GENERAL SIGNIFICANCEAtomistic insights emerging from detailed simulations of Ras in solution and in bilayers may be the key to unlock the secret that to date prevented development of selective anti-Ras inhibitors for cancer therapy.
A great deal has been learned over the last several decades about the function of Ras proteins in solution and membrane environments. While much of this knowledge has been derived from a plethora of experimental techniques, computer simulations have also played a substantial role.Our goal here is to summarize the contribution of molecular simulations to our current understanding of normal and aberrant Ras function. We focus on lessons from molecular dynamics simulations in aqueous and membrane environments.The central message is that a close interaction between theory and simulation on the one hand and cell-biological, spectroscopic and other experimental approaches on the other has played, and will likely continue to play, a vital role in Ras research.Atomistic insights emerging from detailed simulations of Ras in solution and in bilayers may be the key to unlock the secret that to date prevented development of selective anti-Ras inhibitors for cancer therapy.
BACKGROUND: A great deal has been learned over the last several decades about the function of Ras proteins in solution and membrane environments. While much of this knowledge has been derived from a plethora of experimental techniques, computer simulations have also played a substantial role. SCOPE OF REVIEW: Our goal here is to summarize the contribution of molecular simulations to our current understanding of normal and aberrant Ras function. We focus on lessons from molecular dynamics simulations in aqueous and membrane environments. MAJOR CONCLUSIONS: The central message is that a close interaction between theory and simulation on the one hand and cell-biological, spectroscopic and other experimental approaches on the other has played, and will likely continue to play, a vital role in Ras research. GENERAL SIGNIFICANCE: Atomistic insights emerging from detailed simulations of Ras in solution and in bilayers may be the key to unlock the secret that to date prevented development of selective anti-Ras inhibitors for cancer therapy.
A great deal has been learned over the last several decades about the function of Ras proteins in solution and membrane environments. While much of this knowledge has been derived from a plethora of experimental techniques, computer simulations have also played a substantial role. Our goal here is to summarize the contribution of molecular simulations to our current understanding of normal and aberrant Ras function. We focus on lessons from molecular dynamics simulations in aqueous and membrane environments. The central message is that a close interaction between theory and simulation on the one hand and cell-biological, spectroscopic and other experimental approaches on the other has played, and will likely continue to play, a vital role in Ras research. Atomistic insights emerging from detailed simulations of Ras in solution and in bilayers may be the key to unlock the secret that to date prevented development of selective anti-Ras inhibitors for cancer therapy. •Contribution of molecular simulations to the study of Ras GTPases•Multi-scale molecular dynamics simulations of Ras in solution and in membrane•Dynamics plays an important role in the biological activity of Ras proteins.•Implications of simulations and protein motion for anti-cancer Ras inhibitors
Author Prakash, Priyanka
Gorfe, Alemayehu A.
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  email: Alemayehu.G.Abebe@uth.tmc.edu
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Issue 11
Keywords Molecular dynamics
Oncogenic Ras
Membrane binding
Clustering
Protein motion
Advanced simulation
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Snippet A great deal has been learned over the last several decades about the function of Ras proteins in solution and membrane environments. While much of this...
BACKGROUND: A great deal has been learned over the last several decades about the function of Ras proteins in solution and membrane environments. While much of...
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SubjectTerms Advanced simulation
Cell Membrane - metabolism
Clustering
computer simulation
Humans
Membrane binding
Molecular dynamics
Molecular Dynamics Simulation
Oncogenic Ras
Protein motion
proteins
ras Proteins - chemistry
ras Proteins - metabolism
Solutions
spectroscopy
therapeutics
Title Lessons from computer simulations of Ras proteins in solution and in membrane
URI https://dx.doi.org/10.1016/j.bbagen.2013.07.024
https://www.ncbi.nlm.nih.gov/pubmed/23906604
https://www.proquest.com/docview/1436563579
https://www.proquest.com/docview/2000084365
https://pubmed.ncbi.nlm.nih.gov/PMC3825463
Volume 1830
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