↓ Skip to main content

Probing the wild-type HRas activation mechanism using steered molecular dynamics, understanding the energy barrier and role of water in the activation

Overview of attention for article published in European Biophysics Journal, January 2014
Altmetric Badge

Mentioned by

twitter
1 tweeter

Citations

dimensions_citation
7 Dimensions

Readers on

mendeley
14 Mendeley
Title
Probing the wild-type HRas activation mechanism using steered molecular dynamics, understanding the energy barrier and role of water in the activation
Published in
European Biophysics Journal, January 2014
DOI 10.1007/s00249-014-0942-4
Pubmed ID
Authors

Neeru Sharma, Uddhavesh Sonavane, Rajendra Joshi

Abstract

Ras is one of the most common oncogenes in human cancers. It belongs to a family of GTPases that functions as binary conformational switches by timely switching of their conformations from GDP to GTP and vice versa. It attains the final active state structure via an intermediate GTP-bound state. The transition between these states is a millisecond-time-scale event. This makes studying this mechanism beyond the scope of classical molecular dynamics. In the present study, we describe the activation pathway of the HRas protein complex along the distance-based reaction coordinate using steered molecular dynamics. Approximately ~720 ns of MD simulations using CMD and SMD was performed. We demonstrated the change in orientation and arrangement of the two switch regions and the role of various hydrogen bonds during the activation process. The weighted histogram analysis method was also performed, and the potential of mean force was calculated between the inactive and active via the intermediate state (state 1) of HRas. The study indicates that water seems to play a crucial role in the activation process and to transfer the HRas protein from its intermediate state to the fully active state. The implications of our study hereby suggest that the HRas activation mechanism is a multistep process. It starts from the inactive state to an intermediate state 1 followed by trapping of water molecules and flipping of the Thr35 residue to form a fully active state (state 2). This state 2 also comprises Gly60, Thr35, GTP, Mg(2+) and water-forming stable interactions.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 14 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Italy 1 7%
Unknown 13 93%

Demographic breakdown

Readers by professional status Count As %
Student > Master 5 36%
Other 3 21%
Researcher 2 14%
Student > Postgraduate 1 7%
Student > Ph. D. Student 1 7%
Other 2 14%
Readers by discipline Count As %
Agricultural and Biological Sciences 5 36%
Chemistry 4 29%
Computer Science 1 7%
Biochemistry, Genetics and Molecular Biology 1 7%
Unspecified 1 7%
Other 2 14%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 November 2014.
All research outputs
#10,837,481
of 12,225,829 outputs
Outputs from European Biophysics Journal
#234
of 289 outputs
Outputs of similar age
#188,485
of 231,438 outputs
Outputs of similar age from European Biophysics Journal
#3
of 5 outputs
Altmetric has tracked 12,225,829 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 289 research outputs from this source. They receive a mean Attention Score of 2.7. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 231,438 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 5 others from the same source and published within six weeks on either side of this one. This one has scored higher than 2 of them.