TY - JOUR T1 - The Role of Conserved Waters in Conformational Transitions of Q61H K-ras A1 - Prakash, Priyanka A1 - Sayyed-Ahmad, Abdallah A1 - Gorfe, Alemayehu A. Y1 - 2012/02/16 N2 - Author Summary K-ras belongs to the Ras family of G-proteins that regulate cell proliferation and development. To execute its function, K-ras adopts different conformational states when it is active and inactive. In addition to these two states, it samples many transient intermediate conformations as it makes the transition from one state to the other. Mutations that affect the population of these states can cause cancer or developmental disorder. Using simulation approaches, here we show that a number of water molecules buried within the structure of an oncogenic K-ras protein modulate the distribution of its conformational states. Moreover, a detailed analysis based on two novel structural parameters revealed the existence of long-range water-mediated interactions that facilitate a dynamic coupling between the two lobes of the protein. These findings pave the way for a dynamics-guided strategy to inhibit abnormal Ras signaling. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 8 IS - 2 UR - https://doi.org/10.1371/journal.pcbi.1002394 SP - e1002394 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1002394 ER -