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

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.