The PCA Page

This is a selection of publications about the development and applications of Protein-fragment Complementation Assays (PCA) by topic. Choices of topics reflect our own interests, but if you have suggestions for other topics and references, send them to us and we’ll be happy to include them. This list is largely thanks to the efforts of Bram Stynen. A recent perspective on the history and advances in PCA is available here.

Reviews on PCA
  • Michnick, S.W. Three decades of protein-fragment complementation. Nat Rev Mol Cell Biol (2024). https://doi.org/10.1038/s41580-024-00813-0
  • Michnick, S. W., Ear, P. H., Manderson, E. N., Remy, I. & Stefan, E. Universal strategies in research and drug discovery based on protein-fragment complementation assays. Nat Rev Drug Discov 6, 569-582 (2007). https://doi.org/10.1038/nrd2311
  • Wehr, M. C. & Rossner, M. J. Split protein biosensor assays in molecular pharmacological studies. Drug Discov Today 21, 415-429 (2016). https://doi.org/10.1016/j.drudis.2015.11.004
  • Romei, M. G. & Boxer, S. G. Split Green Fluorescent Proteins: Scope, Limitations, and Outlook. Annual Review of Biophysics 48, 19-44 (2019). https://doi.org/https://doi.org/10.1146/annurev-biophys-051013-022846
  • Shekhawat, S.S., and Ghosh, I. (2011). Split-protein systems: beyond binary protein-protein interactions. Curr Opin Chem Biol 15, 789-797. 10.1016/j.cbpa.2011.10.014.
  • Wang, T., Yang, N., Liang, C., Xu, H., An, Y., Xiao, S., Zheng, M., Liu, L., Wang, G., and Nie, L. (2020). Detecting Protein-Protein Interaction Based on Protein Fragment Complementation Assay. Curr Protein Pept Sci 21, 598-610. 10.2174/1389203721666200213102829.
  • Blaszczak, E., Lazarewicz, N., Sudevan, A., Wysocki, R., and Rabut, G. (2021). Protein-fragment complementation assays for large-scale analysis of protein–protein interactions. Biochemical Society Transactions 49, 1337-1348. 10.1042/bst20201058.
Inspiration, early developments, and design of PCA
  • Johnsson, N., and Varshavsky, A. (1994). Split ubiquitin as a sensor of protein interactions in vivo. Proceedings of the National Academy of Sciences of the United States of America 91, 10340-10344. 10.1073/pnas.91.22.10340.
  • Pelletier, J.N., and Michnick, S.W. (1997). A Protein Complementation Assay for Detection of Protein-Protein Interactions in vivo. Protein Engineering 10, 89.
  • Pelletier, J.N., Campbell-Valois, F.X., and Michnick, S.W. (1998). Oligomerization domain-directed reassembly of active dihydrofolate reductase from rationally designed fragments. Proceedings of the National Academy of Sciences of the United States of America 95, 12141-12146. 10.1073/pnas.95.21.12141.
  • Michnick, S., Remy, I., Campbell-Valois, F., Vallee-Belisle, A., and Pelletier, J. (2000). Detection of protein-protein interactions by protein fragment complementation strategies. Methods Enzymol 328, 208-230.
  • Remy, I. & Michnick, S. W. Clonal selection and in vivo quantitation of protein interactions with protein-fragment complementation assays. Proceedings of the National Academy of Sciences of the United States of America 96, 5394-5399 (1999). https://doi.org/10.1073/pnas.96.10.5394
  • Pelletier, J., Arndt, K., Pluckthun, A. & Michnick, S. An in vivo library-versus-library selection of optimized protein-protein interactions. Nature Biotechnology 17, 683-690 (1999).
  • Remy, I., Wilson, I.A., and Michnick, S.W. (1999). Erythropoietin receptor activation by a ligand-induced conformation change. Science (New York, N.Y.) 283, 990-993. 10.1126/science.283.5404.990.
  • Dolberg, T.B., Meger, A.T., Boucher, J.D., Corcoran, W.K., Schauer, E.E., Prybutok, A.N., Raman, S., and Leonard, J.N. (2021). Computation-guided optimization of split protein systems. Nat Chem Biol. 10.1038/s41589-020-00729-8.

A zoological garden of PCAs
  • Johnsson, N., and Varshavsky, A. (1994). Split ubiquitin as a sensor of protein interactions in vivo. Proceedings of the National Academy of Sciences of the United States of America 91, 10340-10344. 10.1073/pnas.91.22.10340.
  • Pelletier, J.N., and Michnick, S.W. (1997). A Protein Complementation Assay for Detection of Protein-Protein Interactions in vivo. Protein Engineering 10, 89.
  • Karimova, G., Pidoux, J., Ullmann, A., and Ladant, D. (1998). A bacterial two-hybrid system based on a reconstituted signal transduction pathway. Proceedings of the National Academy of Sciences of the United States of America 95, 5752-5756. 10.1073/pnas.95.10.5752.
  • Pelletier, J.N., Campbell-Valois, F.X., and Michnick, S.W. (1998). Oligomerization domain-directed reassembly of active dihydrofolate reductase from rationally designed fragments. Proceedings of the National Academy of Sciences of the United States of America 95, 12141-12146. 10.1073/pnas.95.21.12141.
  • Stagljar, I., Korostensky, C., Johnsson, N., and te Heesen, S. (1998). A genetic system based on split-ubiquitin for the analysis of interactions between membrane proteins in vivo. Proceedings of the National Academy of Sciences of the United States of America 95, 5187-5192. 10.1073/pnas.95.9.5187.
  • Ghosh, I., Hamilton, A.D., and Regan, L. (2000). Antiparallel Leucine Zipper-Directed Protein Reassembly: Application to the Green Fluorescent Protein. Journal of the American Chemical Society 122, 5658-5659. 10.1021/ja994421w.
  • Michnick, S., Remy, I., Campbell-Valois, F., Vallee-Belisle, A., and Pelletier, J. (2000). Detection of protein-protein interactions by protein fragment complementation strategies (Glycinamide Ribonucleotide (GAR) Transformylase; Aminoglycoside and Hygromycin B Phosphotransferases). Methods Enzymol 328, 208-230.
  • Laser, H., Bongards, C., Schüller, J., Heck, S., Johnsson, N., and Lehming, N. (2000). A new screen for protein interactions reveals that the Saccharomyces cerevisiae high mobility group proteins Nhp6A/B are involved in the regulation of the GAL1 promoter. Proceedings of the National Academy of Sciences of the United States of America 97, 13732-13737. 10.1073/pnas.250400997.
  • Ozawa, T., Nogami, S., Sato, M., Ohya, Y., and Umezawa, Y. (2000). A fluorescent indicator for detecting protein-protein interactions in vivo based on protein splicing. Analytical chemistry 72, 5151-5157. 10.1021/ac000617z.
  • Rojo-Niersbach, E., Morley, D., Heck, S., and Lehming, N. (2000). A new method for the selection of protein interactions in mammalian cells. The Biochemical journal 348 Pt 3, 585-590.
  • Chen, L., Pradhan, S., and Evans, T.C. (2001). Herbicide resistance from a divided EPSPS protein: The split Synechocystis DnaE intein as an in vivo affinity domain. Gene 263, 39-48. 10.1016/S0378-1119(00)00568-0.
  • Galarneau, A., Primeau, M., Trudeau, L.-E., and Michnick, S.W. (2002). Beta-lactamase protein fragment complementation assays as in vivo and in vitro sensors of protein protein interactions. Nature biotechnology 20, 619-622. 10.1038/nbt0602-619.
  • Paulmurugan, R., Umezawa, Y., and Gambhir, S.S. (2002). Noninvasive imaging of protein-protein interactions in living subjects by using reporter protein complementation and reconstitution strategies. Proceedings of the National Academy of Sciences of the United States of America 99, 15608-15613. 10.1073/pnas.242594299.
  • Wehrman, T., Kleaveland, B., Her, J.-H., Balint, R.F., and Blau, H.M. (2002). Protein-protein interactions monitored in mammalian cells via complementation of beta -lactamase enzyme fragments. Proceedings of the National Academy of Sciences of the United States of America 99, 3469-3474. 10.1073/pnas.062043699.
  • Hu, C.-D., and Kerppola, T.K. (2003). Simultaneous visualization of multiple protein interactions in living cells using multicolor fluorescence complementation analysis. Nature biotechnology 21, 539-545. 10.1038/nbt816.
  • Kaihara, A., Kawai, Y., Sato, M., Ozawa, T., and Umezawa, Y. (2003). Locating a protein-protein interaction in living cells via split Renilla luciferase complementation. Analytical chemistry 75, 4176-4181. 10.1021/ac0300800.
  • Paulmurugan, R., and Gambhir, S.S. (2003). Monitoring protein-protein interactions using split synthetic renilla luciferase protein-fragment-assisted complementation. Analytical chemistry 75, 1584-1589. 10.1021/ac020731c.
  • Luker, K.E., Smith, M.C.P., Luker, G.D., Gammon, S.T., Piwnica-Worms, H., and Piwnica-Worms, D. (2004). Kinetics of regulated protein-protein interactions revealed with firefly luciferase complementation imaging in cells and living animals. Proceedings of the National Academy of Sciences of the United States of America 101, 12288-12293. 10.1073/pnas.0404041101.
  • Tafelmeyer, P., Johnsson, N., and Johnsson, K. (2004). Transforming a 8-barrel enzyme into a split-protein sensor through directed evolution. Chemistry and Biology 11, 681-689. 10.1016/j.chembiol.2004.02.026.
  • Zhang, S., Ma, C., and Chalfie, M. (2004). Combinatorial marking of cells and organelles with reconstituted fluorescent proteins. Cell 119, 137-144. 10.1016/j.cell.2004.09.012.
  • Paschon, D.E., Patel, Z.S., and Ostermeier, M. (2005). Enhanced catalytic efficiency of aminoglycoside phosphotransferase (3???)-IIa achieved through protein fragmentation and reassembly. Journal of Molecular Biology 353, 26-37. 10.1016/j.jmb.2005.08.026.
  • Wehr, M.C., Laage, R., Bolz, U., Fischer, T.M., Grünewald, S., Scheek, S., Bach, A., Nave, K.-A., and Rossner, M.J. (2006). Monitoring regulated protein-protein interactions using split TEV. Nature methods 3, 985-993. 10.1038/nmeth967.
  • Stefan, E., Aquin, S., Berger, N., Landry, C.R., Nyfeler, B., Bouvier, M., and Michnick, S.W. (2007). Quantification of dynamic protein complexes using Renilla luciferase fragment complementation applied to protein kinase A activities in vivo. Proceedings of the National Academy of Sciences of the United States of America 104, 16916-16921. 10.1073/pnas.0704257104.
  • Chen, H., Zou, Y., Shang, Y., Lin, H., Wang, Y., Cai, R., Tang, X., and Zhou, J.-M. (2008). Firefly luciferase complementation imaging assay for protein-protein interactions in plants. Plant physiology 146, 368-376. 10.1104/pp.107.111740.
  • Ear, P.H., and Michnick, S.W. (2009). A general life-death selection strategy for dissecting protein functions. Nature methods 6, 813-816. 10.1038/nmeth.1389.
  • Hida, N., Awais, M., Takeuchi, M., Ueno, N., Tashiro, M., Takagi, C., Singh, T., Hayashi, M., Ohmiya, Y., and Ozawa, T. (2009). High-sensitivity real-time imaging of dual protein-protein interactions in living subjects using multicolor luciferases. PLoS ONE 4. 10.1371/journal.pone.0005868.
  • Kodama, Y., and Wada, M. (2009). Simultaneous visualization of two protein complexes in a single plant cell using multicolor fluorescence complementation analysis. Plant molecular biology 70, 211-217. 10.1007/s11103-009-9467-0.
  • Rahim, G., Bischof, S., Kessler, F., and Agne, B. (2009). In vivo interaction between atToc33 and atToc159 GTP-binding domains demonstrated in a plant split-ubiquitin system. Journal of experimental botany 60, 257-267. 10.1093/jxb/ern283.
  • Massoud, T.F., Paulmurugan, R., and Gambhir, S.S. (2010). A molecularly engineered split reporter for imaging protein-protein interactions with positron emission tomography. Nature medicine 16, 921-926. 10.1038/nm.2185.
  • Müller, M.M., Kries, H., Csuhai, E., Kast, P., and Hilvert, D. (2010). Design, selection, and characterization of a split chorismate mutase. Protein science : a publication of the Protein Society 19, 1000-1010. 10.1002/pro.377.
  • Nguyen, P.Q., and Silberg, J.J. (2010). A selection that reports on protein-protein interactions within a thermophilic bacterium. Protein engineering, design & selection : PEDS 23, 529-536. 10.1093/protein/gzq024.
  • Li, J.F., Bush, J., Xiong, Y., Li, L., and McCormack, M. (2011). Large-scale protein-protein interaction analysis in Arabidopsis mesophyll protoplasts by split firefly luciferase complementation. PLoS ONE 6. 10.1371/journal.pone.0027364.
  • Mie, M., Naoki, T., Uchida, K., and Kobatake, E. (2012). Development of a split SNAP-tag protein complementation assay for visualization of protein-protein interactions in living cells. The Analyst 137, 4760-4765. 10.1039/c2an35762c.
  • Camacho-Soto, K., Castillo-Montoya, J., Tye, B., and Ghosh, I. (2014). Ligand-gated split-kinases. Journal of the American Chemical Society 136, 3995-4002. 10.1021/ja4130803.
  • Dai, X., Zhu, M., and Wang, Y.-P. (2014). Circular permutation of E. coli EPSP synthase: increased inhibitor resistance, improved catalytic activity, and an indicator for protein fragment complementation. Chemical communications (Cambridge, England) 50, 1830-1832. 10.1039/c3cc48722a.
  • O’Brien, S.P., and Delisa, M.P. (2014). Split-Cre recombinase effectively monitors protein-protein interactions in living bacteria. Biotechnology journal 9, 355-361. 10.1002/biot.201300462.
  • Tchekanda, E., Sivanesan, D., and Michnick, S.W. (2014). An infrared reporter to detect spatiotemporal dynamics of protein-protein interactions. Nat Methods 11, 641-644. 10.1038/nmeth.2934.
  • Zetsche, B., Volz, S.E., and Zhang, F. (2015). A split-Cas9 architecture for inducible genome editing and transcription modulation. Nat Biotechnol 33, 139-142. 10.1038/nbt.3149.
  • Guo, Z., Murphy, L., Stein, V., Johnston, W.A., Alcala-Perez, S., and Alexandrov, K. (2016). Engineered PQQ-Glucose Dehydrogenase as a Universal Biosensor Platform. J Am Chem Soc 138, 10108-10111. 10.1021/jacs.6b06342.
  • Martell, J.D., Yamagata, M., Deerinck, T.J., Phan, S., Kwa, C.G., Ellisman, M.H., Sanes, J.R., and Ting, A.Y. (2016). A split horseradish peroxidase for the detection of intercellular protein-protein interactions and sensitive visualization of synapses. Nat Biotechnol 34, 774-780. 10.1038/nbt.3563.
  • Mie, M., Naoki, T., and Kobatake, E. (2016). Development of a Split SNAP-CLIP Double Labeling System for Tracking Proteins Following Dissociation from Protein-Protein Complexes in Living Cells. Anal Chem 88, 8166-8171. 10.1021/acs.analchem.6b01906.
  • Dixon, A.S., Schwinn, M.K., Hall, M.P., Zimmerman, K., Otto, P., Lubben, T.H., Butler, B.L., Binkowski, B.F., Machleidt, T., Kirkland, T.A., et al. (2016). NanoLuc Complementation Reporter Optimized for Accurate Measurement of Protein Interactions in Cells. ACS Chem Biol 11, 400-408. 10.1021/acschembio.5b00753.
  • Diaz, J.E., Morgan, C.W., Minogue, C.E., Hebert, A.S., Coon, J.J., and Wells, J.A. (2017). A Split-Abl Kinase for Direct Activation in Cells. Cell Chemical Biology 24, 1250-1258.e1254. 10.1016/j.chembiol.2017.08.007.
  • Chernov, K.G., Neuvonen, M., Brock, I., Ikonen, E., and Verkhusha, V.V. (2017). Introducing inducible fluorescent split cholesterol oxidase to mammalian cells. J Biol Chem 292, 8811-8822. 10.1074/jbc.M116.761718.
  • De Munter, S., Görnemann, J., Derua, R., Lesage, B., Qian, J., Heroes, E., Waelkens, E., Van Eynde, A., Beullens, M., and Bollen, M. (2017). Split-BioID: a proximity biotinylation assay for dimerization-dependent protein interactions. FEBS Lett 591, 415-424. 10.1002/1873-3468.12548.
  • Pu, J., Dewey, J.A., Hadji, A., LaBelle, J.L., and Dickinson, B.C. (2017). RNA Polymerase Tags To Monitor Multidimensional Protein-Protein Interactions Reveal Pharmacological Engagement of Bcl-2 Proteins. J Am Chem Soc 139, 11964-11972. 10.1021/jacs.7b06152.
  • Pu, J., Zinkus-Boltz, J., and Dickinson, B.C. (2017). Evolution of a split RNA polymerase as a versatile biosensor platform. Nat Chem Biol 13, 432-438. 10.1038/nchembio.2299.
  • Schopp, I.M., Amaya Ramirez, C.C., Debeljak, J., Kreibich, E., Skribbe, M., Wild, K., and Béthune, J. (2017). Split-BioID a conditional proteomics approach to monitor the composition of spatiotemporally defined protein complexes. Nat Commun 8, 15690. 10.1038/ncomms15690.
  • Xue, M., Hou, J., Wang, L., Cheng, D., Lu, J., Zheng, L., and Xu, T. (2017). Optimizing the fragment complementation of APEX2 for detection of specific protein-protein interactions in live cells. Scientific Reports 7, 12039. 10.1038/s41598-017-12365-9.
  • Zeng, Y., Jones, A.M., Thomas, E.E., Nassif, B., Silberg, J.J., and Segatori, L. (2018). A Split Transcriptional Repressor That Links Protein Solubility to an Orthogonal Genetic Circuit. ACS Synth Biol 7, 2126-2138. 10.1021/acssynbio.8b00129.
  • Golob-Urbanc, A., Rajcevic, U., Strmsek, Z., and Jerala, R. (2019). Design of split superantigen fusion proteins for cancer immunotherapy. J Biol Chem. 10.1074/jbc.RA118.006742.
  • Han, Y., Branon, T.C., Martell, J.D., Boassa, D., Shechner, D., Ellisman, M.H., and Ting, A. (2019). Directed Evolution of Split APEX2 Peroxidase. ACS Chem Biol 14, 619-635. 10.1021/acschembio.8b00919.
  • Boassa, D., Lemieux, S.P., Lev-Ram, V., Hu, J., Xiong, Q., Phan, S., Mackey, M., Ramachandra, R., Peace, R.E., Adams, S.R., et al. (2019). Split-miniSOG for Spatially Detecting Intracellular Protein-Protein Interactions by Correlated Light and Electron Microscopy. Cell Chemical Biology 26, 1407-1416.e1405. 10.1016/j.chembiol.2019.07.007.
  • Ni, Y., Arts, R., and Merkx, M. (2019). Ratiometric Bioluminescent Sensor Proteins Based on Intramolecular Split Luciferase Complementation. ACS Sens 4, 20-25. 10.1021/acssensors.8b01381.
  • Rozbeh, R., and Forchhammer, K. (2021). Split NanoLuc technology allows quantitation of interactions between PII protein and its receptors with unprecedented sensitivity and reveals transient interactions. Scientific Reports 11, 12535. 10.1038/s41598-021-91856-2.
  • Chen, M., Yan, C., Qin, F., and Zhang, X.-E. (2022). Near-Infrared Luciferase Complementation Assay with Enhanced Bioluminescence for Studying Protein–Protein Interactions and Drug Evaluation Under Physiological Conditions. Analytical Chemistry 94, 13700-13709. 10.1021/acs.analchem.2c01238.
  • Wei, R., Yu, Z., Ding, L., Lu, Z., Yao, K., Zhang, H., Huang, B., He, M., and Ma, L. (2025). Improved split prime editors enable efficient in vivo genome editing. Cell reports 44. 10.1016/j.celrep.2024.115144.
  • Jillette, N., Du, M., Zhu, J. J., Cardoz, P. & Cheng, A. W. Split selectable markers. Nature communications 10, 4968 (2019). https://doi.org/10.1038/s41467-019-12891-2

Topology, Dynamics and Evolution of PPI networks

  • Remy, I., and Michnick, S.W. (2001). Visualization of biochemical networks in living cells. Proceedings of the National Academy of Sciences of the United States of America 98, 7678-7683. 10.1073/pnas.131216098. 
  • Miller, J. et al. Large-scale identification of yeast integral membrane protein interactions. Proc Natl Acad Sci U S A 102, 12123-12128 (2005).  
  • Macdonald, M. L. et al. Identifying off-target effects and hidden phenotypes of drugs in human cells. Nat Chem Biol 2, 329-337 (2006).  
  • Remy, I. & Michnick, S. W. A cDNA library functional screening strategy based on fluorescent protein complementation assays to identify novel components of signaling pathways. Methods 32, 381-388 (2004).  
  • Messier, V., Zenklusen, D. & Michnick, S. W. A nutrient-responsive pathway that determines M phase timing through control of B-cyclin mRNA stability. Cell 153, 1080-1093 (2013). https://doi.org/10.1016/j.cell.2013.04.035 
  • Celaj, A. et al. Quantitative analysis of protein interaction network dynamics in yeast. Mol Syst Biol 13, 934 (2017). https://doi.org/10.15252/msb.20177532 
  • Schlecht, U., Liu, Z., Blundell, J. R., St Onge, R. P. & Levy, S. F. A scalable double-barcode sequencing platform for characterization of dynamic protein-protein interactions. Nat Commun 8, 15586 (2017). https://doi.org/10.1038/ncomms15586 
  • Rochette, S., Gagnon-Arsenault, I., Diss, G., and Landry, C.R. (2013). Modulation of the yeast protein interactome in response to DNA damage. Journal of proteomics. 10.1016/j.jprot.2013.11.007. 
  • Lev, I. et al. Reverse PCA, a systematic approach for identifying genes important for the physical interaction between protein pairs. PLoS genetics 9, e1003838 (2013). https://doi.org/10.1371/journal.pgen.1003838 
  • Diss, G., Dubé, A. K., Boutin, J., Gagnon-Arsenault, I. & Landry, C. R. A systematic approach for the genetic dissection of protein complexes in living cells. Cell reports 3, 2155-2167 (2013). https://doi.org/10.1016/j.celrep.2013.05.004 
  • Diss, G., Gagnon-Arsenault, I., Dion-Cote, A.M., Vignaud, H., Ascencio, D.I., Berger, C.M., and Landry, C.R. (2017). Gene duplication can impart fragility, not robustness, in the yeast protein interaction network. Science 355, 630-634. 10.1126/science.aai7685. 
  • Filteau, M., Vignaud, H., Rochette, S., Diss, G., Chretien, A.E., Berger, C.M., and Landry, C.R. (2016). Multi-scale perturbations of protein interactomes reveal their mechanisms of regulation, robustness and insights into genotype-phenotype maps. Brief Funct Genomics 15, 130-137. 10.1093/bfgp/elv043. 
  • Rochette, S., Gagnon-Arsenault, I., Diss, G., and Landry, C.R. (2013). Modulation of the yeast protein interactome in response to DNA damage. Journal of proteomics. 10.1016/j.jprot.2013.11.007. 
  • Diss, G., Dubé, A.K., Boutin, J., Gagnon-Arsenault, I., and Landry, C.R. (2013). A systematic approach for the genetic dissection of protein complexes in living cells. Cell reports 3, 2155-2167. 10.1016/j.celrep.2013.05.004. 
  • Tarassov, K., Messier, V., Landry, C.R., Radinovic, S., Serna Molina, M.M., Shames, I., Malitskaya, Y., Vogel, J., Bussey, H., and Michnick, S.W. (2008). An in vivo map of the yeast protein interactome. Science (New York, N.Y.) 320, 1465-1470. 10.1126/science.1153878. 
  • Ear, P.H., Booth, M.J., Abd-Rabbo, D., Kowarzyk Moreno, J., Hall, C., Chen, D., Vogel, J., and Michnick, S.W. (2013). Dissection of Cdk1-cyclin complexes in vivo. Proceedings of the National Academy of Sciences of the United States of America 110, 15716-15721. 10.1073/pnas.1305420110. 
  • Li, J.F., Bush, J., Xiong, Y., Li, L., and McCormack, M. (2011). Large-scale protein-protein interaction analysis in Arabidopsis mesophyll protoplasts by split firefly luciferase complementation. PLoS ONE 6. 10.1371/journal.pone.0027364. 
  • Lee, O.-H., Kim, H., He, Q., Baek, H.J., Yang, D., Chen, L.-Y., Liang, J., Chae, H.K., Safari, A., Liu, D., and Songyang, Z. (2011). Genome-wide YFP fluorescence complementation screen identifies new regulators for telomere signaling in human cells. Molecular & cellular proteomics : MCP 10, M110.001628. 10.1074/mcp.M110.001628. 
  • Lazarewicz, N., Le Dez, G., Cerjani, R., Runeshaw, L., Meurer, M., Knop, M., Wysocki, R., and Rabut, G. (2024). Accurate and sensitive interactome profiling using a quantitative protein-fragment complementation assay. Cell Reports Methods 4.
PCA in Drug Screening

  • Fox, L.M., and Saravolatz, L.D. (2005). Nitazoxanide: a new thiazolide antiparasitic agent. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 40, 1173-1180. 10.1086/428839. 
  • Hashimoto, J., Watanabe, T., Seki, T., Karasawa, S., Izumikawa, M., Seki, T., Iemura, S.-I., Natsume, T., Nomura, N., Goshima, N., et al. (2009). Novel in vitro protein fragment complementation assay applicable to high-throughput screening in a 1536-well format. Journal of biomolecular screening 14, 970-979. 10.1177/1087057109341406. 
  • Acerra, N., Kad, N.M., and Mason, J.M. (2013). Combining intracellular selection with protein-fragment complementation to derive Aβ interacting peptides. Protein engineering, design & selection : PEDS 26, 463-470. 10.1093/protein/gzt021. 
  • Dai, J.-P., Zhao, X.-F., Zeng, J., Wan, Q.-Y., Yang, J.-C., Li, W.-Z., Chen, X.-X., Wang, G.-F., and Li, K.-S. (2013). Drug screening for autophagy inhibitors based on the dissociation of Beclin1-Bcl2 complex using BiFC technique and mechanism of eugenol on anti-influenza A virus activity. PloS one 8, e61026. 10.1371/journal.pone.0061026. 
  • Fan-Minogue, H., Bodapati, S., Solow-Cordero, D., Fan, A., Paulmurugan, R., Massoud, T.F., Felsher, D.W., and Gambhir, S.S. (2013). A c-Myc activation sensor-based high-throughput drug screening identifies an antineoplastic effect of nitazoxanide. Molecular cancer therapeutics 12, 1896-1905. 10.1158/1535-7163.MCT-12-1243. 
  • Galbán, S., Jeon, Y.H., Bowman, B.M., Stevenson, J., Sebolt, K.A., Sharkey, L.M., Lafferty, M., Hoff, B.A., Butler, B.L., Wigdal, S.S., et al. (2013). Imaging proteolytic activity in live cells and animal models. PloS one 8, e66248. 10.1371/journal.pone.0066248. 
  • He, J., Niu, X., Hu, C., Zhang, H., Guo, Y., Ge, Y., Wang, G., and Jiang, Y. (2013). Expression and purification of recombinant NRL-Hsp90α and Cdc37-CRL proteins for in vitro Hsp90/Cdc37 inhibitors screening. Protein expression and purification 92, 119-127. 10.1016/j.pep.2013.09.007. 
  • Shinjo, S., Tashiro, E., and Imoto, M. (2013). Establishment of a new detection system for the dimerization of IRE1α by BiFC assay. Bioscience, biotechnology, and biochemistry 77, 1333-1336. 
  • Acerra, N., Kad, N.M., Griffith, D.A., Ott, S., Crowther, D.C., and Mason, J.M. (2014). Retro-inversal of Intracellular Selected β-Amyloid-Interacting Peptides: Implications for a Novel Alzheimer’s Disease Treatment. Biochemistry. 10.1021/bi5001257. 
  • Arkin, M.R., Tang, Y., and Wells, J.A. (2014). Small-molecule inhibitors of protein-protein interactions: progressing toward the reality. Chem Biol 21, 1102-1114. 10.1016/j.chembiol.2014.09.001. 
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Energetics of Gene Variations on PPI and Protein Stability

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PCA in Synthetic Biology

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