Ras Conformational Ensembles, Allostery, and Signaling

The phosphoinositide 3-kinase pathway

Cantley, L. C. (2002) · Science · doi:10.1126/science.296.5573.1655 · Cited by 5,621

ras GENES

Barbacid, M. (1987) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.56.070187.004023 · Cited by 3,885

The GTPase superfamily: conserved structure and molecular mechanism

Bourne, H. R., Sanders, D. A., & McCormick, F. (1991) · Nature · doi:10.1038/349117a0 · Cited by 3,392

Targeting RAS signalling pathways in cancer therapy

Downward, J. (2003) · Nature reviews. Cancer · doi:10.1038/nrc969 · Cited by 3,354

The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism

Engelman, J. A., Luo, J., & Cantley, L. C. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1879 · Cited by 3,330

The Energy Landscapes and Motions of Proteins

Frauenfelder, H., Sligar, S. G., & Wolynes, P. G. (1991) · Science · doi:10.1126/science.1749933 · Cited by 3,250

Targeting the phosphoinositide 3-kinase pathway in cancer

Liu, P., Cheng, H.-L. M., Roberts, T. M., & Zhao, J. J. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2926 · Cited by 2,785

K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions

Ostrem, J. M., Peters, U., Sos, M. L., Wells, J. A., & Shokat, K. M. (2013) · Nature · doi:10.1038/nature12796 · Cited by 2,557

Small GTP-Binding Proteins

Takai, Y., Sasaki, T., & Matozaki, T. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.1.153 · Cited by 2,511

COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer

Forbes, S. A., Bindal, N., Bamford, S., Cole, C., Kok, C. Y., Beare, D., Jia, M., Shepherd, R., Leung, K., Menzies, A., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkq929 · Cited by 2,278

KRAS mutant colon cancer-targeted induction of ferroptosis via photocatalytic activation of BiVO4-embedded silica nano with cascadic downregulation of GPX4/xCT axis

Jiang, Y., Jenjob, R., Ryu, D., Shen, Z., & Yang, S. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.06.024 · Cited by 2

G12 mutations rewire allosteric communication at the Ras–RalGDS interface

Demirbas, E., Jang, H., Kosoglu, K., Nussinov, R., Gürsoy, A., & Keskin, Ö. (2026) · Biophysical Journal · doi:10.1016/j.bpj.2026.01.053 · Cited by 2

Computational dissection of allosteric inhibition of the SH2 domain of Bcr-Abl kinase by the monobody inhibitor AS25

Ji, M., Zheng, G., Li, X., Zhang, Z., Jv, G., Wang, X., & Wang, J. (2017) · Journal of Molecular Modeling · doi:10.1007/s00894-017-3353-5 · Cited by 2

Analysis of correlated mutations in Ras G-domain

Pathak, E. (2017) · Bioinformation · doi:10.6026/97320630013174 · Cited by 2

Synthesis, Biological Evaluation, and Binding Mode of a New Class of Oncogenic K‐Ras4b Inhibitors

Jeuken, S., Shkura, O., Röger, M., Brickau, V., Choidas, A., Degenhart, C., Gülden, D., Klebl, B., Koch, U., Stoll, R., et al. (2022) · ChemMedChem · doi:10.1002/cmdc.202200392 · Cited by 2

Multiplexed imaging for probing RAS-RAF interactions in living cells

Ahmad, M., & Movileanu, L. (2023) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2023.184173 · Cited by 2

The structural basis of the oncogenic mutant K-Ras4B homodimersPreprint

Kosoglu, K., Omur, M. E., Jang, H., Nussinov, R., Keskin, Ö., & Gürsoy, A. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.09.07.285783 · Cited by 2

Ras S89D mutation induced allosteric changes that promoted its nucleotide exchange and signaling activation

Li, Y., Huang, W., Guo, L., & Sun, Q. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.139538 · Cited by 1

KRASG12D in Cancer: Structural Insights, Signaling Pathways, and Progress in Targeted Inhibitor Design

Zhou, J., Fang, Z., Zhang, W., Rao, G.-W., & Zheng, Q. (2025) · Mini-Reviews in Organic Chemistry · doi:10.2174/0118756298391640250731025705 · Cited by 1

Drought stress responses revealed by genomic and transcriptomic analyses of two macrofungi (Inonotus hispidus and Inocutis levis) from Populus euphratica

Zhou, M., Lv, M., Wu, D., Gao, N., Xu, T.-M., Sun, Y.-F., & Cui, B. (2025) · IMA Fungus · doi:10.3897/imafungus.16.163859 · Cited by 1

Molecular basis of Rab43 inactivation by RN-Tre in endocytic trafficking unveils a general Rab-GAP recognition mechanism

Wang, J., Liu, T., Zhang, Z., & Yan, W. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.149561 · Cited by 1

Elucidating conformational dynamics of GDP/GTP-KRAS complexes caused by mutations from the switch domain I through Gaussian accelerated molecular dynamics simulations

Shi, S., Liu, A., & Guo, Y. (2026) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2025.2610685 · Cited by 1

Dynamic binding of HRas·GTP to the allosteric site of Sos investigated by solution NMR

Li, B., Wang, H., Wang, H. Z., Fang, M., & Long, D. (2025) · JUSTC · doi:10.52396/justc-2024-0132 · Cited by 1

Computationally Efficient Network Models Successfully Predict Allosteric Sites of SARS ‐ CoV ‐2 Main Protease and Reveal Its Dynamic Allostery

Yuce, M., & Kürkçüoğlu, Ö. (2026) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.70122 · Cited by 1

Structure–Activity Relationship Analysis of Macrocyclic Peptide RAS Inhibitors: Spotlight on the Solvent-Exposed Region

Chiyoda, A., Matsuo, A., Yamano, T., & Tanada, M. (2026) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.6c00122 · Cited by 1

Turbo Analytics: Applications of Big Data and HPC in Drug Discovery

Joshi, R., Sonavane, U., Jani, V., Saxena, A., Koulgi, S., N, M. U. V., Sharma, N., Malviya, S. S., Ramakrishnan, E. P., Gavane, V., et al. (2019) · Challenges and advances in computational chemistry and physics · doi:10.1007/978-3-030-05282-9_11 · Cited by 1

Elucidating Structural Details of Ras-Effector Interactions

Muratcioğlu, S., & Acuner, S. E. (2019) · International Journal of Advances in Engineering and Pure Sciences · doi:10.7240/jeps.528662 · Cited by 1

Extending the Lifetime of Native GTP‐Bound Ras for Site‐Resolved NMR Measurements: Quantifying the Allosteric Dynamics

Chen, X., Yao, H., Wang, H., Mao, Y., Liu, D., & Long, D. (2019) · Angewandte Chemie · doi:10.1002/ange.201812902 · Cited by 1

Investigating the effects of cysteine-118 oxidation on G12D KRas structure and dynamics: insights from MD simulations

Salamh, S., & Sayyed–Ahmad, A. (2023) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2023.2238080 · Cited by 1

Mutations influence the conformational dynamics of the GDP/KRAS complex

Shen, C., Yin, J., Wang, M., Yu, Z., Xu, X. Y., Zhou, Z.-S., Hu, Y., Xia, C., & Hu, G. (2024) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2024.2331627 · Cited by 1

Site-directed antibodies targeting driver mutations of the KRAS protein

Li, X., Mendez, Q. M., Chapados, C. D., Acca, F. E., Driscoll, H., Oliveira, J., Liu, J., Jones, K. S., Ferguson, M., Wallace, R. L., et al. (2025) · New Biotechnology · doi:10.1016/j.nbt.2025.04.003 · Cited by 1

Oncogenic G12D mutation alters local conformations and dynamics of K-RasPreprint

Vatansever, S., Erman, B., & Gumus, Z. H. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/178483 · Cited by 1

Data from Delineating the RAS Conformational Landscape

Parker, M. I., Meyer, J. E., Golemis, E. A., & Dunbrack (2023) · doi:10.1158/0008-5472.c.6513960.v1 · Cited by 1

Engineered subtilisin protease degrades active KRAS in cancer cells, leading to differential cell targetingPreprint

Goldstein, M. E., Chu, B., Carillo, K. J., Orban, J. P., Toth, E. A., & Fuerst, T. R. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.03.04.709402 · Cited by 1

Data from Delineating the RAS Conformational Landscape

Parker, M. I., Meyer, J. E., Golemis, E. A., & Dunbrack (2023) · doi:10.1158/0008-5472.c.6513960

Caractérisation des réseaux d’interactions protéiques associés aux mutations oncogéniques principales retrouvées dans le cancer du poumon non à petites cellules

Béganton, B. (2017) · theses.fr (ABES) · doi:10.70675/9b9e7703zbda1z43b1za320zf3f7dc2f71dd

Genomics-based Precision Medicine for Patients with Cancer

van de Haar, J. (2021) · Utrecht University Repository (Utrecht University) · doi:10.33540/946

Az ELTE ’SzintPlusz’ Tématerületi Kiválósági Program első éve: 2019-2020

Perczel, A. (2021) · Magyar kémiai folyóirat, Kémiai közlemények · doi:10.24100/mkf.2021.02.58

The Ras Dimer StructurePreprint

Rudack, T., Teuber, C., Scherlo, M., Güldenhaupt, J., Schartner, J., Lübben, M., Klare, J. P., Gerwert, K. B., & Kötting, C. (2021) · ChemRxiv · doi:10.26434/chemrxiv.14039810

Modeling and Simulation of Lipid Membranes

Marti, J., & Calero, C. (2022) · MDPI eBooks · doi:10.3390/books978-3-0365-4938-5

Evaluation of K-Ras4B dimer interfaces and the role of Raf effectorsPreprint

Chatzigoulas, A., Andreadelis, I., Doerr, S., Lamprakis, C., Theodoropoulou, A., Manchester, J. I., Velez‐Vega, C., Duca, J. S., & Cournia, Z. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.10.04.510804

The Emerging Role of Molecular Dynamics Simulations in Cancer Research

Friedman, R. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-821978-2.00088-x

Unraveling the Significance of Mg2+ Dependency and Nucleotide Binding Specificity of H-RAS

Tagad, A., & Patwari, G. N. (2024) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.3c06998

Allosteric interactions in KRas and HRas: studies of KRas/Calmodulin and HRas/Raf-RBD

Ojeda, M. (2023) · Digital Repository Service (Northeastern University) · doi:10.17760/d20621550

Design, Synthesis and Biological Evaluation of Pan-Kras Inhibitors Derived from Pyrazolo[3,4-D]PyrimidinePreprint

Hu, Y., Lin, X., Zhu, J., Lin, Y., Zhang, Y., Liu, C., & Jiang, F. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5281075

Oscillatory signal decoding within the ERK cascadePreprint

Ganesan, A., Lee, H. N., Tenner, B., Mehta, S., Levchenko, A., & Zhang, J. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.24.666680

USING CHEMICAL AND PROTEOMICS APPROACHES TO STUDY THE FUNCTIONS OF SIRT6 AND KRAS

Zhang, X. (2017) · eCommons (Cornell University) · doi:10.7298/x4ff3qjs

Preliminary Characterization of K-Ras via Nuclear Magnetic Resonance

Cantu, D. V. (2019) · OhioLink ETD Center (Ohio Library and Information Network)

Synthese von Lipopeptiden und Proteinkonjugaten zur Funktion des N-Ras-Proteins

Krois, D. (2026) · Springer eBooks · doi:10.1007/978-3-662-72214-5_9

The Neomorphic Chemistry of KRAS Autophosphorylation Is Dynamically Regulated by Active Site Conformation

Johnson, C. W., Oladimeji, R., O’Donohue, E., & Haigis, K. M. (2026) · ACS Chemical Biology · doi:10.1021/acschembio.6c00157

Synthèse et optimisation de nouveaux dérivés anti-mélanome 4-phényl-2-aminothiazole ciblant GRP78 pour contourner les mécanismes de résistances

Millet, A. (2016) · theses.fr (ABES) · doi:10.70675/0d504cc4za41bz4a62z9f83zc23bcfa0b934

Synthesis, biological evaluation, and mechanism investigation of multisubstituted quinazoline analogues as prospective inhibitors of KRAS G12D

Liu, X., Nie, Q., Zhang, Y.-S., He, J., Sun, X.-R., Cao, W.-J., Zhang, H.-Y., Zhang, J., & Chen, S. (2026) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2026.109875

Navigating high-order protein fitness landscapes via deep learning on directed evolution trajectories

Song, C., Ma, L., Xu, Y., Xu, Y., Zhang, Q., Liu, Y., Song, C., & Lin, Y. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2520561123

Synthesis of Lipopeptides and Protein Conjugates for the Function of the N-Ras Protein

Krois, D. (2026) · Springer eBooks · doi:10.1007/978-3-662-73573-2_9

Discovery and Characterization of RP04340 : A Highly Potent and Orally Active Pan-KRAS PROTAC Degrader

Ji, X. L., Du, Y., Zhang, Q., Zong, B., Du, K., He, X., Wu, G., Liang, C., 胡磬遥, Zhang, Y., et al. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c01832

A chemigenetic endogenous Ras activity biosensor for live-cell pharmacology

Weeks, R., Zhou, D. R., Frei, M. S., & Zhang, J. (2026) · Nature Chemical Biology · doi:10.1038/s41589-026-02276-0

A programmable lipid-triggered allosteric site modulates LC3 LIR receptor binding activity

Gahlot, D., Jesu Castin, E., Mathur, S. C., Das, D., Kumar, A., Arun, A., Gain, C., Sharma, M., Pal, R. K., Jain, N., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-76697-9

Engineered subtilisin protease degrades active KRAS in cancer cells leading to differential cell targetingPreprint

Fuerst, T. R., Goldstein, M., Chu, B., Carillo, K. J., Orban, J. P., & Toth, E. (2026) · Research Square · doi:10.21203/rs.3.rs-10438702/v1

Regulation of Membrane Association and Downstream Effector Interaction of K-Ras by Its Hypervariable Region

Trifan, A., Omidi-Ardali, H., Vermaas, J. V., Rudack, T., & Tajkhorshid, E. (2026) · Membranes · doi:10.3390/membranes16090304

Multimodal allostery in a single-domain proteinPreprint

Ma, Y., Jin, Q., Lehner, B., & Weng, C. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.14.750605

Switch dynamics and activity of GTP-bound HRAS affected by R97 mutations at allosteric helix α3

Li, Y., Wang, J., 沈建忠, Longlong, R. E. N., & Chen, J. (2026) · Physical Chemistry Chemical Physics · doi:10.1039/d6cp03485c

Efficient detection of cryptic pockets on challenging drug targets using MD-free co-vibrational modesPreprint

Szalai, T. V., Bajusz, D., Orgován, Z., Ábrányi‐Balogh, P., Gadanecz, M., Imre, T., Grant, E. K., Bush, J. T., Kolossváry, I., & Keserű, G. M. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.07.757394

BindingDB Entry 50010796: Discovery of Novel PDEδ Degraders for the Treatment of KRAS Mutant Colorectal Cancer.

BindingDB (2021) · UC San Diego · doi:10.7270/q2rn3cfh

BindingDB Entry 50019341: Ras superfamily GTPase activating proteins in cancer: Potential therapeutic targets?

BindingDB (2024) · UC San Diego · doi:10.7270/q2m61qmd

BindingDB Entry 50020071: Discovery of Novel PDEδ Autophagic Degraders: A Case Study of Autophagy-Tethering Compound (ATTEC).

BindingDB (2024) · UC San Diego · doi:10.7270/q2bv7n19

BindingDB Entry 50009378: Allosteric Modulator Discovery: From Serendipity to Structure-Based Design.

BindingDB (2021) · UC San Diego · doi:10.7270/q2c53q9m

BindingDB Entry 50021822: Structure-activity relationships of middle-size cyclic peptides, KRAS inhibitors derived from an mRNA display.

BindingDB (2025) · UC San Diego · doi:10.7270/q2xw4qgf

BindingDB Entry 50006764: Small Molecule Allosteric Modulators of G-Protein-Coupled Receptors: Drug-Target Interactions.

BindingDB (2021) · UC San Diego · doi:10.7270/q2h70k2m

BindingDB Entry 50011605: Small-Molecule Inhibitors Directly Targeting KRAS as Anticancer Therapeutics.

BindingDB (2022) · UC San Diego · doi:10.7270/q2t1578s

Ras Signaling: Allostery, Conformation, and Function

Nussinov, R., & Jang, H. (2018) · Biophysical Journal · doi:10.1016/j.bpj.2017.11.2216

The Allosteric Switch and Conformational States in Ras GTPase Affected by Small Molecules

Johnson, C. W., & Mattos, C. (2013) · The Enzymes · doi:10.1016/b978-0-12-416749-0.00003-8 · Cited by 35

Relation between the Conformational Heterogeneity and Reaction Cycle of Ras: Molecular Simulation of Ras

Kobayashi, C., & Saito, S. (2010) · Biophysical Journal · doi:10.1016/j.bpj.2010.09.063 · Cited by 33

Divergent Mechanisms Activating RAS and Small GTPases Through Post-translational Modification

Osaka, N., Hirota, Y., Ito, D., Ikeda, Y., Kamata, R., Fujii, Y., Chirasani, V. R., Campbell, S. L., Takeuchi, K., Senda, T., et al. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.707439 · Cited by 35

Allosteric Modulation of Ras-GTP Is Linked to Signal Transduction through RAF Kinase

Buhrman, G., Kumar, V. S. S., Cirit, M., Haugh, J. M., & Mattos, C. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.193854 · Cited by 88