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• W4220954810 endingPage "7665" @default.
• W4220954810 startingPage "7653" @default.
• W4220954810 abstract "As the hub of major signaling pathways, Ras proteins are implicated in 19% of tumor-caused cancers due to perturbations in their conformational and/or catalytic properties. Despite numerous studies, the functions of the conformational substates for the most important isoform, KRas, remain elusive. In this work, we perform an extensive simulation analysis on the conformational landscape of KRas in its various chemical states during the GTP hydrolysis cycle: the reactant state KRasGTP·Mg2+, the intermediate state KRasGDP·Pi·Mg2+ and the product state KRasGDP·Mg2+. The results from enhanced sampling simulations reveal that State 1 of KRasGTP·Mg2+ has multiple stable substates in solution, one of which might account for interacting with GEFs. State 2 of KRasGTP·Mg2+ features two substates Tyr32in and Tyr32out, which are poised to interact with effectors and GAPs, respectively. For the intermediate state KRasGDP·Pi·Mg2+, Gln61 and Pi are found to assume a broad set of conformations, which might account for the weak oncogenic effect of Gln61 mutations in KRas in contrast to the situation in HRas and NRas. Finally, the product state KRasGDP·Mg2+ has more than two stable substates in solution, pointing to a conformation-selection mechanism for complexation with GEFs. Based on these results, some specific inhibition strategies for targeting the binding sites of the high-energy substates of KRas during GTP hydrolysis are discussed." @default.
• W4220954810 created "2022-04-03" @default.
• W4220954810 creator A5005627824 @default.
• W4220954810 creator A5013649577 @default.
• W4220954810 creator A5017541012 @default.
• W4220954810 creator A5036163052 @default.
• W4220954810 creator A5036789652 @default.
• W4220954810 creator A5083210325 @default.
• W4220954810 date "2022-01-01" @default.
• W4220954810 modified "2023-10-16" @default.
• W4220954810 title "Identification of functional substates of KRas during GTP hydrolysis with enhanced sampling simulations" @default.
• W4220954810 cites W1622452078 @default.
• W4220954810 cites W1781036264 @default.
• W4220954810 cites W1918986430 @default.
• W4220954810 cites W1960357661 @default.
• W4220954810 cites W1964930474 @default.
• W4220954810 cites W1969836007 @default.
• W4220954810 cites W1976170436 @default.
• W4220954810 cites W1985981634 @default.
• W4220954810 cites W1987365716 @default.
• W4220954810 cites W1989233227 @default.
• W4220954810 cites W1989747730 @default.
• W4220954810 cites W1991215291 @default.
• W4220954810 cites W1992864103 @default.
• W4220954810 cites W1993735775 @default.
• W4220954810 cites W2004275564 @default.
• W4220954810 cites W2018019331 @default.
• W4220954810 cites W2023309667 @default.
• W4220954810 cites W2024944232 @default.
• W4220954810 cites W2025458374 @default.
• W4220954810 cites W2027357567 @default.
• W4220954810 cites W2031842520 @default.
• W4220954810 cites W2036935837 @default.
• W4220954810 cites W2038532826 @default.
• W4220954810 cites W2038989070 @default.
• W4220954810 cites W2040809566 @default.
• W4220954810 cites W2043124575 @default.
• W4220954810 cites W2053423866 @default.
• W4220954810 cites W2054396228 @default.
• W4220954810 cites W2058834594 @default.
• W4220954810 cites W2063254536 @default.
• W4220954810 cites W2063484479 @default.
• W4220954810 cites W2067174909 @default.
• W4220954810 cites W2073967748 @default.
• W4220954810 cites W2077873773 @default.
• W4220954810 cites W2083164919 @default.
• W4220954810 cites W2083410297 @default.
• W4220954810 cites W2083695927 @default.
• W4220954810 cites W2096929343 @default.
• W4220954810 cites W2101724097 @default.
• W4220954810 cites W2103945336 @default.
• W4220954810 cites W2112154906 @default.
• W4220954810 cites W2128339707 @default.
• W4220954810 cites W2132629607 @default.
• W4220954810 cites W2135184154 @default.
• W4220954810 cites W2142454421 @default.
• W4220954810 cites W2146926552 @default.
• W4220954810 cites W2158219305 @default.
• W4220954810 cites W2159615687 @default.
• W4220954810 cites W2160284454 @default.
• W4220954810 cites W2165097702 @default.
• W4220954810 cites W2167980930 @default.
• W4220954810 cites W2168033476 @default.
• W4220954810 cites W2260312731 @default.
• W4220954810 cites W2282990014 @default.
• W4220954810 cites W2298480233 @default.
• W4220954810 cites W2321991740 @default.
• W4220954810 cites W2328575291 @default.
• W4220954810 cites W2332712348 @default.
• W4220954810 cites W2404280981 @default.
• W4220954810 cites W2461456119 @default.
• W4220954810 cites W2464027273 @default.
• W4220954810 cites W2612664817 @default.
• W4220954810 cites W2717068414 @default.
• W4220954810 cites W2741710452 @default.
• W4220954810 cites W2769412055 @default.
• W4220954810 cites W2785187242 @default.
• W4220954810 cites W2793589905 @default.
• W4220954810 cites W2799702558 @default.
• W4220954810 cites W2886738135 @default.
• W4220954810 cites W2893018770 @default.
• W4220954810 cites W2912277053 @default.
• W4220954810 cites W2914874256 @default.
• W4220954810 cites W2942808707 @default.
• W4220954810 cites W2943623664 @default.
• W4220954810 cites W2963086398 @default.
• W4220954810 cites W2964025523 @default.
• W4220954810 cites W2967433676 @default.
• W4220954810 cites W2980433900 @default.
• W4220954810 cites W2982321167 @default.
• W4220954810 cites W3013377779 @default.
• W4220954810 cites W3017122228 @default.
• W4220954810 cites W3041359365 @default.
• W4220954810 cites W3075473545 @default.
• W4220954810 cites W3075491940 @default.
• W4220954810 cites W3134674457 @default.
• W4220954810 cites W3183565205 @default.
• W4220954810 cites W3189465577 @default.

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