84
Views
0
CrossRef citations to date
0
Altmetric
Research Article

Mutations influence the conformational dynamics of the GDP/KRAS complex

, , , , , , , & ORCID Icon show all
Received 22 Jan 2024, Accepted 20 Feb 2024, Published online: 26 Mar 2024

References

  • Ajmal, A., Ali, Y., Khan, A., Wadood, A., & Rehman, A. U. (2023a). Identification of novel peptide inhibitors for the KRas-G12C variant to prevent oncogenic signaling. Journal of Biomolecular Structure & Dynamics, 41(18), 8866–8875. https://doi.org/10.1080/07391102.2022.2138550
  • Ajmal, A., Mahmood, A., Hayat, C., Hakami, M. A., Alotaibi, B. S., Umair, M., Abdalla, A. N., Li, P., He, P., Wadood, A., & Hu, J. (2023b). Computer-assisted drug repurposing for thymidylate kinase drug target in monkeypox virus. Frontiers in Cellular and Infection Microbiology, 13, 1159389. https://doi.org/10.3389/fcimb.2023.1159389
  • Amadei, A., Linssen, A. B. M., & Berendsen, H. J. C. (1993). Essential dynamics of proteins. Proteins, 17(4), 412–425. https://doi.org/10.1002/prot.340170408
  • Anandakrishnan, R., Aguilar, B., & Onufriev, A. V. (2012). H++ 3.0: Automating pK prediction and the preparation of biomolecular structures for atomistic molecular modeling and simulations. Nucleic Acids Research, 40(Web Server issue), W537–W541. https://doi.org/10.1093/nar/gks375
  • Araki, M., Shima, F., Yoshikawa, Y., Muraoka, S., Ijiri, Y., Nagahara, Y., Shirono, T., Kataoka, T., & Tamura, A. (2011). Solution structure of the state 1 conformer of GTP-bound H-Ras protein and distinct dynamic properties between the state 1 and state 2 conformers. The Journal of Biological Chemistry, 286(45), 39644–39653. https://doi.org/10.1074/jbc.M111.227074
  • Bao, H., He, W., & Chen, J. (2023). Exploring conformation changes of Janus kinase 2 pseudokinase mediated by mutations through Gaussian accelerated molecular dynamics and principal component analysis. Journal of Biomolecular Structure & Dynamics, 1–18. https://doi.org/10.1080/07391102.2023.2260486
  • Bera, A. K., Lu, J., Lu, C., Li, L., Gondi, S., Yan, W., Nelson, A., Zhang, G., & Westover, K. D. (2020). GTP hydrolysis is modulated by Arg34 in the RASopathy-associated KRASP34R. Birth Defects Research, 112(10), 708–717. https://doi.org/10.1002/bdr2.1647
  • Bos, J. L., Rehmann, H., & Wittinghofer, A. (2007). GEFs and GAPs: Critical elements in the control of small G proteins. Cell, 129(5), 865–877. https://doi.org/10.1016/j.cell.2007.05.018
  • Bourne, H. R., Sanders, D. A., & McCormick, F. (1990). The GTPase superfamily: A conserved switch for diverse cell functions. Nature, 348(6297), 125–132. https://doi.org/10.1038/348125a0
  • Case, D. A., Cheatham, T. E., Darden, T., Gohlke, H., Luo, R., Merz, K. M., Onufriev, A., Simmerling, C., Wang, B., & Woods, R. J. (2005). The Amber biomolecular simulation programs. Journal of Computational Chemistry, 26(16), 1668–1688. https://doi.org/10.1002/jcc.20290
  • Chen, J., Wang, L., Wang, W., Sun, H., Pang, L., & Bao, H. (2021a). Conformational transformation of switch domains in GDP/K-Ras induced by G13 mutants: An investigation through Gaussian accelerated molecular dynamics simulations and principal component analysis. Computers in Biology and Medicine, 135, 104639. https://doi.org/10.1016/j.compbiomed.2021.104639
  • Chen, J., Zeng, Q., Wang, W., Hu, Q., & Bao, H. (2022a). Q61 mutant-mediated dynamics changes of the GTP-KRAS complex probed by Gaussian accelerated molecular dynamics and free energy landscapes. RSC Advances, 12(3), 1742–1757. https://doi.org/10.1039/D1RA07936K
  • Chen, J., Zeng, Q., Wang, W., Sun, H., & Hu, G. (2022b). Decoding the identification mechanism of an SAM-III Riboswitch on ligands through multiple independent gaussian-accelerated molecular dynamics simulations. Journal of Chemical Information and Modeling, 62(23), 6118–6132. https://doi.org/10.1021/acs.jcim.2c00961
  • Chen, J., Zhang, S., Wang, W., Pang, L., Zhang, Q., & Liu, X. (2021b). Mutation-induced impacts on the switch transformations of the GDP- and GTP-bound K-Ras: Insights from multiple replica Gaussian accelerated molecular dynamics and free energy analysis. Journal of Chemical Information and Modeling, 61(4), 1954–1969. https://doi.org/10.1021/acs.jcim.0c01470
  • Chen, J., Zhang, S., Zeng, Q., Wang, W., Zhang, Q., & Liu, X. (2022c). Free energy profiles relating with conformational transition of the switch domains induced by G12 mutations in GTP-Bound KRAS. Frontiers in Molecular Biosciences, 9, 912518. https://doi.org/10.3389/fmolb.2022.912518
  • Cruz-Migoni, A., Canning, P., Quevedo, C. E., Bataille, C. J. R., Bery, N., Miller, A., Russell, A. J., Phillips, S. E. V., Carr, S. B., & Rabbitts, T. H. (2019). Structure-based development of new RAS-effector inhibitors from a combination of active and inactive RAS-binding compounds. Proceedings of the National Academy of Sciences of the United States of America, 116(7), 2545–2550. https://doi.org/10.1073/pnas.1811360116
  • Eren, M., Tuncbag, N., Jang, H., Nussinov, R., Gursoy, A., & Keskin, O. (2021). Normal mode analysis of KRas4B reveals partner specific dynamics. The Journal of Physical Chemistry. B, 125(20), 5210–5221. https://doi.org/10.1021/acs.jpcb.1c00891
  • Essmann, U., Perera, L., Berkowitz, M. L., Darden, T., Lee, H., & Pedersen, L. G. (1995). A smooth particle mesh Ewald method. The Journal of Chemical Physics, 103(19), 8577–8593. https://doi.org/10.1063/1.470117
  • Fernández-Medarde, A., & Santos, E. (2011). Ras in cancer and developmental diseases. Genes & Cancer, 2(3), 344–358. https://doi.org/10.1177/1947601911411084
  • Gao, Y., Zhu, T., & Chen, J. (2018). Exploring drug-resistant mechanisms of I84V mutation in HIV-1 protease toward different inhibitors by thermodynamics integration and solvated interaction energy method. Chemical Physics Letters. 706, 400–408. https://doi.org/10.1016/j.cplett.2018.06.040
  • Götz, A. W., Williamson, M. J., Xu, D., Poole, D., Le Grand, S., & Walker, R. C. (2012). Routine microsecond molecular dynamics simulations with AMBER on GPUs. 1. Generalized born. Journal of Chemical Theory and Computation, 8(5), 1542–1555. https://doi.org/10.1021/ct200909j
  • Grant, B. J., Gorfe, A. A., & McCammon, J. A. (2009). Ras conformational Switching: Simulating nucleotide-dependent conformational transitions with accelerated molecular dynamics. PLoS Computational Biology, 5(3), e1000325. https://doi.org/10.1371/journal.pcbi.1000325
  • Hayward, S., Kitao, A., & Go, N. (1995). Harmonicity and anharmonicity in protein dynamics: A normal mode analysis and principal component analysis. Proteins, 23(2), 177–186. https://doi.org/10.1002/prot.340230207
  • Henzler-Wildman, K., & Kern, D. (2007). Dynamic personalities of proteins. Nature, 450(7172), 964–972. https://doi.org/10.1038/nature06522
  • Hobbs, G. A., Der, C. J., & Rossman, K. L. (2016). RAS isoforms and mutations in cancer at a glance. Journal of Cell Science, 129(7), 1287–1292. https://doi.org/10.1242/jcs.182873
  • Humphrey, W., Dalke, A., & Schulten, K. (1996). VMD: Visual molecular dynamics. Journal of Molecular Graphics, 14(1), 33–38. https://doi.org/10.1016/0263-7855(96)00018-5
  • Hu, G., Zhang, Y., Yu, Z., Cui, T., & Cui, W. (2023). Dynamical characterization and multiple unbinding paths of two PreQ1 ligands in one pocket. Physical Chemistry Chemical Physics: PCCP, 25(35), 24004–24015. https://doi.org/10.1039/D3CP03142J
  • Hu, G., & Zhou, H.-X. (2021). Binding free energy decomposition and multiple unbinding paths of buried ligands in a PreQ1 riboswitch. PLoS Computational Biology, 17(11), e1009603. https://doi.org/10.1371/journal.pcbi.1009603
  • Hu, G., & Zhou, H.-X. (2023). Magnesium ions mediate ligand binding and conformational transition of the SAM/SAH riboswitch. Communications Biology, 6(1), 791. https://doi.org/10.1038/s42003-023-05175-5
  • Ichiye, T., & Karplus, M. (1991). Collective motions in proteins: A covariance analysis of atomic fluctuations in molecular dynamics and normal mode simulations. Proteins, 11(3), 205–217. https://doi.org/10.1002/prot.340110305
  • Izaguirre, J. A., Catarello, D. P., Wozniak, J. M., & Skeel, R. D. (2001). Langevin stabilization of molecular dynamics. The Journal of Chemical Physics, 114(5), 2090–2098. https://doi.org/10.1063/1.1332996
  • Johnson, C. W., Lin, Y.-J., Reid, D., Parker, J., Pavlopoulos, S., Dischinger, P., Graveel, C., Aguirre, A. J., Steensma, M., Haigis, K. M., & Mattos, C. (2019). Isoform-specific destabilization of the active site reveals a molecular mechanism of intrinsic activation of KRas G13D. Cell Reports, 28(6), 1538–1550.e1537. https://doi.org/10.1016/j.celrep.2019.07.026
  • Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W., & Klein, M. L. (1983). Comparison of simple potential functions for simulating liquid water. The Journal of Chemical Physics, 79(2), 926–935. https://doi.org/10.1063/1.445869
  • Joung, I. S, & T. E. Cheatham III. (2008). Determination of alkali and halide monovalent ion parameters for use in explicitly solvated biomolecular simulations. The Journal of Physical Chemistry. B, 112(30), 9020–9041. https://doi.org/10.1021/jp8001614
  • Joung, I. S, & T. E. Cheatham III (2009). Molecular dynamics simulations of the dynamic and energetic properties of alkali and halide ions using water-model-specific ion parameters. The Journal of Physical Chemistry. B, 113(40), 13279–13290. https://doi.org/10.1021/jp902584c
  • Kessler, D., Gmachl, M., Mantoulidis, A., Martin, L. J., Zoephel, A., Mayer, M., Gollner, A., Covini, D., Fischer, S., Gerstberger, T., Gmaschitz, T., Goodwin, C., Greb, P., Häring, D., Hela, W., Hoffmann, J., Karolyi-Oezguer, J., Knesl, P., Kornigg, S., … McConnell, D. B. (2019). Drugging an undruggable pocket on KRAS. Proceedings of the National Academy of Sciences of the United States of America, 116(32), 15823–15829. https://doi.org/10.1073/pnas.1904529116
  • Kolch, W., Berta, D., & Rosta, E. (2023). Dynamic regulation of RAS and RAS signaling. The Biochemical Journal, 480(1), 1–23. https://doi.org/10.1042/bcj20220234
  • Liang, S., Liu, X., Zhang, S., Li, M., Zhang, Q., & Chen, J. (2022). Binding mechanism of inhibitors to SARS-CoV-2 main protease deciphered by multiple replica molecular dynamics simulations. Physical Chemistry Chemical Physics: PCCP, 24(3), 1743–1759. https://doi.org/10.1039/D1CP04361G
  • Li, M., Liu, X., Zhang, S., Liang, S., Zhang, Q., & Chen, J. (2022). Deciphering the binding mechanism of inhibitors of the SARS-CoV-2 main protease through multiple replica accelerated molecular dynamics simulations and free energy landscapes. Physical Chemistry Chemical Physics: PCCP, 24(36), 22129–22143. https://doi.org/10.1039/D2CP03446H
  • Li, P., Roberts, B. P., Chakravorty, D. K., & Merz, K. M. Jr. (2013). Rational design of particle mesh ewald compatible lennard-jones parameters for +2 metal cations in explicit solvent. Journal of Chemical Theory and Computation, 9(6), 2733–2748. https://doi.org/10.1021/ct400146w
  • Lu, S., Jang, H., Muratcioglu, S., Gursoy, A., Keskin, O., Nussinov, R., & Zhang, J. (2016). Ras conformational ensembles, allostery, and signaling. Chemical Reviews, 116(11), 6607–6665. https://doi.org/10.1021/acs.chemrev.5b00542
  • McGregor, L. M., Jenkins, M. L., Kerwin, C., Burke, J. E., & Shokat, K. M. (2017). Expanding the scope of electrophiles capable of targeting K-Ras oncogenes. Biochemistry, 56(25), 3178–3183. https://doi.org/10.1021/acs.biochem.7b00271
  • Meagher, K. L., Redman, L. T., & Carlson, H. A. (2003). Development of polyphosphate parameters for use with the AMBER force field. Journal of Computational Chemistry, 24(9), 1016–1025. https://doi.org/10.1002/jcc.10262
  • Miao, Y., Feher, V. A., & McCammon, J. A. (2015). Gaussian accelerated molecular dynamics: Unconstrained enhanced sampling and free energy calculation. Journal of Chemical Theory and Computation, 11(8), 3584–3595. https://doi.org/10.1021/acs.jctc.5b00436
  • Miao, Y., & McCammon, J. A. (2016). Graded activation and free energy landscapes of a muscarinic G-protein–coupled receptor. Proceedings of the National Academy of Sciences of the United States of America, 113(43), 12162–12167. https://doi.org/10.1073/pnas.1614538113
  • Miao, Y., Sinko, W., Pierce, L., Bucher, D., Walker, R. C., & McCammon, J. A. (2014). Improved reweighting of accelerated molecular dynamics simulations for free energy calculation. Journal of Chemical Theory and Computation, 10(7), 2677–2689. https://doi.org/10.1021/ct500090q
  • Milburn, M. V., Tong, L., deVos, A. M., Brünger, A., Yamaizumi, Z., Nishimura, S., & Kim, S.-H. (1990). Molecular switch for signal transduction: Structural differences between active and inactive forms of protooncogenic ras proteins. Science (New York, N.Y.), 247(4945), 939–945. https://doi.org/10.1126/science.2406906
  • Mo, S. P., Coulson, J. M., & Prior, I. A. (2018). RAS variant signalling. Biochemical Society Transactions, 46(5), 1325–1332. https://doi.org/10.1042/bst20180173
  • Narayan, B., Kiel, C., & Buchete, N.-V. (2023). Classification of GTP-dependent K-Ras4B active and inactive conformational states. The Journal of Chemical Physics, 158(9), 091104. https://doi.org/10.1063/5.0139181
  • Nnadi, C. I., Jenkins, M. L., Gentile, D. R., Bateman, L. A., Zaidman, D., Balius, T. E., Nomura, D. K., Burke, J. E., Shokat, K. M., & London, N. (2018). Novel K-Ras G12C Switch-II covalent binders destabilize Ras and accelerate nucleotide exchange. Journal of Chemical Information and Modeling, 58(2), 464–471. https://doi.org/10.1021/acs.jcim.7b00399
  • Ostrem, J. M., Peters, U., Sos, M. L., Wells, J. A., & Shokat, K. M. (2013). K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature, 503(7477), 548–551. https://doi.org/10.1038/nature12796
  • Peng, X., Zhang, Y., Li, Y., Liu, Q., Chu, H., Zhang, D., & Li, G. (2018). Integrating multiple accelerated molecular dynamics to improve accuracy of free energy calculations. Journal of Chemical Theory and Computation, 14(3), 1216–1227. https://doi.org/10.1021/acs.jctc.7b01211
  • Pierce, L. C. T., Salomon-Ferrer, R., Augusto, F., de Oliveira, C., McCammon, J. A., & Walker, R. C. (2012). Routine access to millisecond time scale events with accelerated molecular dynamics. Journal of Chemical Theory and Computation, 8(9), 2997–3002. https://doi.org/10.1021/ct300284c
  • Roe, D. R, & T. E. Cheatham III (2013). PTRAJ and CPPTRAJ: Software for processing and analysis of molecular dynamics trajectory data. Journal of Chemical Theory and Computation, 9(7), 3084–3095. https://doi.org/10.1021/ct400341p
  • Ryckaert, J.-P., Ciccotti, G., & Berendsen, H. J. C. (1977). Numerical integration of the Cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes. Journal of Computational Physics. 23(3), 327–341. https://doi.org/10.1016/0021-9991(77)90098-5
  • Salomon-Ferrer, R., Case, D. A., & Walker, R. C. (2013a). An overview of the Amber biomolecular simulation package. WIREs Computational Molecular Science, 3(2), 198–210. https://doi.org/10.1002/wcms.1121
  • Salomon-Ferrer, R., Götz, A. W., Poole, D., Le Grand, S., & Walker, R. C. (2013b). Routine microsecond molecular dynamics simulations with AMBER on GPUs. 2. Explicit solvent particle Mesh Ewald. Journal of Chemical Theory and Computation, 9(9), 3878–3888. https://doi.org/10.1021/ct400314y
  • Sayyed-Ahmad, A., Prakash, P., & Gorfe, A. A. (2017). Distinct dynamics and interaction patterns in H- and K-Ras oncogenic P-loop mutants. Proteins, 85(9), 1618–1632. https://doi.org/10.1002/prot.25317
  • Shi, S., Zheng, L., Ren, Y., & Wang, Z. (2023). Impacts of mutations in the P-loop on conformational alterations of KRAS investigated with Gaussian accelerated molecular dynamics simulations. Molecules (Basel, Switzerland), 28(7), 2886. https://doi.org/10.3390/molecules28072886
  • Sun, Q., Burke, J. P., Phan, J., Burns, M. C., Olejniczak, E. T., Waterson, A. G., Lee, T., Rossanese, O. W., & Fesik, S. W. (2012). Discovery of small molecules that bind to k-ras and inhibit sos-mediated activation. Angewandte Chemie (International ed. in English), 51(25), 6140–6143. https://doi.org/10.1002/anie.201201358
  • Sun, Z., Gong, Z., Xia, F., & He, X. (2021a). Ion dynamics and selectivity of Nav channels from molecular dynamics simulation. Chemical Physics. 548, 111245. https://doi.org/10.1016/j.chemphys.2021.111245
  • Sun, Z., Huai, Z., He, Q., & Liu, Z. (2021b). A general picture of Cucurbit[8]uril Host–guest binding. Journal of Chemical Information and Modeling, 61(12), 6107–6134. https://doi.org/10.1021/acs.jcim.1c01208
  • Sun, H., Li, Y., Shen, M., Tian, S., Xu, L., Pan, P., Guan, Y., & Hou, T. (2014a). Assessing the performance of MM/PBSA and MM/GBSA methods. 5. Improved docking performance using high solute dielectric constant MM/GBSA and MM/PBSA rescoring. Physical Chemistry Chemical Physics: PCCP, 16(40), 22035–22045. https://doi.org/10.1039/C4CP03179B
  • Sun, H., Li, Y., Tian, S., Xu, L., & Hou, T. (2014b). Assessing the performance of MM/PBSA and MM/GBSA methods. 4. Accuracies of MM/PBSA and MM/GBSA methodologies evaluated by various simulation protocols using PDBbind data set. Physical Chemistry Chemical Physics: PCCP, 16(31), 16719–16729. https://doi.org/10.1039/C4CP01388C
  • Sun, J., Liu, X., Zhang, S., Li, M., Zhang, Q., & Chen, J. (2023). Molecular insights and optimization strategies for the competitive binding of engineered ACE2 proteins: A multiple replica molecular dynamics study. Physical Chemistry Chemical Physics: PCCP, 25(41), 28479–28496. https://doi.org/10.1039/D3CP03392A
  • Tate, J. G., Bamford, S., Jubb, H. C., Sondka, Z., Beare, D. M., Bindal, N., Boutselakis, H., Cole, C. G., Creatore, C., Dawson, E., Fish, P., Harsha, B., Hathaway, C., Jupe, S. C., Kok, C. Y., Noble, K., Ponting, L., Ramshaw, C. C., Rye, C. E., … Forbes, S. A. (2018). COSMIC: The catalogue of somatic mutations in cancer. Nucleic Acids Research, 47(D1), D941–D947. https://doi.org/10.1093/nar/gky1015
  • Tian, C., Kasavajhala, K., Belfon, K. A. A., Raguette, L., Huang, H., Migues, A. N., Bickel, J., Wang, Y., Pincay, J., Wu, Q., & Simmerling, C. (2020). ff19SB: Amino-acid-specific protein backbone parameters trained against quantum mechanics energy surfaces in solution. Journal of Chemical Theory and Computation, 16(1), 528–552. https://doi.org/10.1021/acs.jctc.9b00591
  • Ting, P. Y., Johnson, C. W., Fang, C., Cao, X., Graeber, T. G., Mattos, C., & Colicelli, J. (2015). Tyrosine phosphorylation of RAS by ABL allosterically enhances effector binding. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 29(9), 3750–3761. https://doi.org/10.1096/fj.15-271510
  • Tran, T. H., Chan, A. H., Young, L. C., Bindu, L., Neale, C., Messing, S., Dharmaiah, S., Taylor, T., Denson, J.-P., Esposito, D., Nissley, D. V., Stephen, A. G., McCormick, F., & Simanshu, D. K. (2021). KRAS interaction with RAF1 RAS-binding domain and cysteine-rich domain provides insights into RAS-mediated RAF activation. Nature Communications, 12(1), 1176. https://doi.org/10.1038/s41467-021-21422-x
  • Wadood, A., Ajmal, A., & Rehman, A. U. (2022). Strategies for targeting KRAS: A challenging drug target. Current Pharmaceutical Design, 28(23), 1897–1901. https://doi.org/10.2174/1381612828666220506144046
  • Wang, J., Arantes, P. R., Bhattarai, A., Hsu, R. V., Pawnikar, S., Huang, Y. ‐M M., Palermo, G., & Miao, Y. (2021). Gaussian accelerated molecular dynamics: Principles and applications. WIREs Computational Molecular Science, 11(5), e1521. https://doi.org/10.1002/wcms.1521
  • Wang, J., & Miao, Y. (2019). Mechanistic insights into specific G protein interactions with adenosine receptors. The Journal of Physical Chemistry. B, 123(30), 6462–6473. https://doi.org/10.1021/acs.jpcb.9b04867
  • Wang, J., & Miao, Y. (2020). Peptide Gaussian accelerated molecular dynamics (Pep-GaMD): Enhanced sampling and free energy and kinetics calculations of peptide binding. The Journal of Chemical Physics, 153(15), 154109. https://doi.org/10.1063/5.0021399
  • Wang, Y., Yang, F., Yan, D., Zeng, Y., Wei, B., Chen, J., & He, W. (2023). Identification mechanism of BACE1 on inhibitors probed by using multiple separate molecular dynamics simulations and comparative calculations of binding free energies. Molecules (Basel, Switzerland), 28(12), 4773. https://doi.org/10.3390/molecules28124773
  • Webb, B., & Sali, A. (2014). Comparative protein structure modeling using modeller, current protocols in bioinformatics. John Wiley & Sons, Inc. pp 2015.2016.2011 − 2015.2016.2032.
  • Xue, W., Wang, P., Tu, G., Yang, F., Zheng, G., Li, X., Li, X., Chen, Y., Yao, X., & Zhu, F. (2018a). Computational identification of the binding mechanism of a triple reuptake inhibitor amitifadine for the treatment of major depressive disorder. Physical Chemistry Chemical Physics: PCCP, 20(9), 6606–6616. https://doi.org/10.1039/C7CP07869B
  • Xue, W., Yang, F., Wang, P., Zheng, G., Chen, Y., Yao, X., & Zhu, F. (2018b). What contributes to serotonin–norepinephrine reuptake inhibitors’ dual-targeting mechanism? The key role of transmembrane domain 6 in human serotonin and norepinephrine transporters revealed by molecular dynamics simulation. ACS Chemical Neuroscience, 9(5), 1128–1140. https://doi.org/10.1021/acschemneuro.7b00490
  • Yan, F., Liu, X., Zhang, S., Su, J., Zhang, Q., & Chen, J. (2018). Molecular dynamics exploration of selectivity of dual inhibitors 5M7, 65X, and 65Z toward fatty acid binding proteins 4 and 5. International Journal of Molecular Sciences, 19(9), 2496. https://doi.org/10.3390/ijms19092496
  • Yang, M. H., Tran, T. H., Hunt, B., Agnor, R., Johnson, C. W., Shui, B., Waybright, T. J., Nowak, J. A., Stephen, A. G., Simanshu, D. K., & Haigis, K. M. (2023). Allosteric regulation of switch-II domain controls KRAS oncogenicity. Cancer Research, 83(19), 3176–3183. https://doi.org/10.1158/0008-5472.can-22-3210
  • Yang, F., Wang, Y., Yan, D., Liu, Z., Wei, B., Chen, J., & He, W. (2023). Binding mechanism of inhibitors to heat shock protein 90 investigated by multiple independent molecular dynamics simulations and prediction of binding free energy. Molecules (Basel, Switzerland), 28(12), 4792. https://doi.org/10.3390/molecules28124792
  • Zhang, Z., Guiley, K. Z., & Shokat, K. M. (2022a). Chemical acylation of an acquired serine suppresses oncogenic signaling of K-Ras(G12S). Nature Chemical Biology, 18(11), 1177–1183. https://doi.org/10.1038/s41589-022-01065-9
  • Zhang, Z., Morstein, J., Ecker, A. K., Guiley, K. Z., & Shokat, K. M. (2022b). Chemoselective covalent modification of K-Ras(G12R) with a small molecule electrophile. Journal of the American Chemical Society, 144(35), 15916–15921. https://doi.org/10.1021/jacs.2c05377
  • Zhang, H., Ni, D., Fan, J., Li, M., Zhang, J., Hua, C., Nussinov, R., & Lu, S. (2022). Markov state models and molecular dynamics simulations reveal the conformational transition of the intrinsically disordered hypervariable region of K-Ras4B to the ordered conformation. Journal of Chemical Information and Modeling, 62(17), 4222–4231. https://doi.org/10.1021/acs.jcim.2c00591
  • Zhou, Z.-W., Ambrogio, C., Bera, A. K., Li, Q., Li, X.-X., Li, L., Son, J., Gondi, S., Li, J., Campbell, E., Jin, H., Okoro, J. J., Xu, C.-X., Janne, P. A., & Westover, K. D. (2020). KRASQ61H preferentially signals through MAPK in a RAF dimer-dependent manner in non–small cell lung cancer. Cancer Research, 80(17), 3719–3731. https://doi.org/10.1158/0008-5472.can-20-0448

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.