Publications

All Bolon Lab publications can be viewed on Google Scholar.

Comprehensive fitness landscape of SARS-CoV-2 M ^pro reveals insights into viral resistance mechanisms                      Flynn J., Samant N., Schneider-Nachum G., Bakan D.T., Yilmaz N.K., Schiffer C.A., Moquin S.A., Dovala D., Bolon D.N.A.,  Elife 2022 11:e77433 PMID 35723575 

Defining the substrate envelope of SARS-CoV-2 main protease to predict and avoid drug resistance                    Shaqra A., Zvornicanin S., Huang Q.Y., Lockbaum G., Knapp M., Tandeske L., Bakan D., Flynn J., Bolon D., Moquin S., Dovala D., Yilmaz N.K., Schiffer, C., Defining the substrate envelope of SARS-CoV-2 main protease to predict and avoid drug resistance. Nature Communications 2022 13:3556. PMID 35729165 

Identification of a permissive secondary mutation that restores the enzymatic activity of oseltamivir resistance mutation H275Y                                                                                                                                                                                    Jiang L., Samant N., Liu P., Somasundaran M., Jensen J.D., Marasco W.A., Kowalik T.F., Schiffer C.A., Finberg R.W., Wang J.P., Bolon D.N.A., J. Vir. 2022, jvi0198221. PMC8941911

Analyses of HIV protease variants at the threshold of viability reveals relationships between processing efficiency and fitness.                                                                                                                                                                                                Schneider-Nachum G., Flynn J., Mavor D., Schiffer C.A., Bolon D.N.A.,  Virus Evolution 2021, 7: veab103. PMC8923237. 

The adaptive potential of the middle domain of yeast Hsp90.
Cote-Hammarlof PA, Fragata I, Flynn J, Mavor D, Zeldovich KB, Bank C, Bolon DNA.
Mol Biol Evol. 2020 Sep 1:msaa211. doi: 10.1093/molbev/msaa211. Online ahead of print.

Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance.
Henes M, Kosovrasti K, Lockbaum GJ, Leidner F, Nachum GS, Nalivaika EA, Bolon DNA, Kurt Yilmaz N, Schiffer CA, Whitfield TW.
Biochemistry. 2019 Sep 3;58(35):3711-3726. doi: 10.1021/acs.biochem.9b00446. Epub 2019 Aug 19.

Picomolar to Micromolar: Elucidating the Role of Distal Mutations in HIV-1 Protease in Conferring Drug Resistance.
Henes M, Lockbaum GJ, Kosovrasti K, Leidner F, Nachum GS, Nalivaika EA, Lee SK, Spielvogel E, Zhou S, Swanstrom R, Bolon DNA, Kurt Yilmaz N, Schiffer CA.
ACS Chem Biol. 2019 Aug 13. doi: 10.1021/acschembio.9b00370. 

Quantifying and understanding the fitness effects of protein mutations: Laboratory versus nature.
Boucher JI, Bolon DNA, Tawfik DS.
Protein Sci. 2019 Mar;28(3):671. doi: 10.1002/pro.3476. No abstract available.

Constrained mutational sampling of amino acids in HIV-1 protease evolution.
Boucher JI, Whitfield TW, Dauphin A, Nachum G, Hollins C 3rd, Zeldovich KB, Swanstrom R, Schiffer CA, Luban J, Bolon DNA.
Mol Biol Evol. 2019 Feb 4. doi: 10.1093/molbev/msz022. 

Mutations in influenza A virus neuraminidase and hemagglutinin confer resistance against a broadly neutralizing hemagglutinin stem antibody.
Prachanronarong KL, Canale AS, Liu P, Somasundaran M, Hou S, Poh YP, Han T, Zhu Q, Renzette N, Zeldovich KB, Kowalik TF, Kurt-Yilmaz N, Jensen JD, Bolon DNA, Marasco WA, Finberg RW, Schiffer CA, Wang JP.
J Virol. 2018 Oct 31. pii: JVI.01639-18. doi: 10.1128/JVI.01639-18.

Extending chemical perturbations of the ubiquitin fitness landscape in a classroom setting reveals new constraints on sequence tolerance.
Mavor D, Barlow KA, Asarnow D, Birman Y, Britain D, Chen W, Green EM, Kenner LR, Mensa B, Morinishi LS, Nelson CA, Poss EM, Suresh P, Tian R, Arhar T, Ary BE, Bauer DP, Bergman ID, Brunetti RM, Chio CM, Dai SA, Dickinson MS, Elledge SK, Helsell CVM, Hendel NL, Kang E, Kern N, Khoroshkin MS, Kirkemo LL, Lewis GR, Lou K, Marin WM, Maxwell AM, McTigue PF, Myers-Turnbull D, Nagy TL, Natale AM, Oltion K, Pourmal S, Reder GK, Rettko NJ, Rohweder PJ, Schwarz DMC, Tan SK, Thomas PV, Tibble RW, Town JP, Tsai MK, Ugur FS, Wassarman DR, Wolff AM, Wu TS, Bogdanoff D, Li J, Thorn KS, O'Conchúir S, Swaney DL, Chow ED, Madhani HD, Redding S, Bolon DN, Kortemme T, DeRisi JL, Kampmann M, Fraser JS.
Biol Open. 2018 Jul 23;7(7).

Pervasive contingency and entrenchment in a billion years of Hsp90 evolution.
Starr TN, Flynn JM, Mishra P, Bolon DNA, Thornton JW.
Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):4453-4458.

Synonymous Mutations at the Beginning of the Influenza A Virus Hemagglutinin Gene Impact Experimental Fitness.
Canale AS, Venev SV, Whitfield TW, Caffrey DR, Marasco WA, Schiffer CA, Kowalik TF, Jensen JD, Finberg RW, Zeldovich KB, Wang JP, Bolon DNA.
J Mol Biol. 2018 Apr 13;430(8):1098-1115.

Evolutionary mechanisms studied through protein fitness landscapes.
Canale AS, Cote-Hammarlof PA, Flynn JM, Bolon DN.
Curr Opin Struct Biol. 2018 Feb;48:141-148.

CRISPR-Cas9-mediated saturated mutagenesis screen predicts clinical drug resistance with improved accuracy.
Ma L, Boucher JI, Paulsen J, Matuszewski S, Eide CA, Ou J, Eickelberg G, Press RD, Zhu LJ, Druker BJ, Branford S, Wolfe SA, Jensen JD, Schiffer CA, Green MR, Bolon DN.
Proc Natl Acad Sci U S A. 2017 Oct 31;114(44):11751-11756.

A synthetic biology approach to probing nucleosome symmetry.
Ichikawa Y, Connelly CF, Appleboim A, Miller TC, Jacobi H, Abshiru NA, Chou HJ, Chen Y, Sharma U, Zheng Y, Thomas PM, Chen HV, Bajaj V, Müller CW, Kelleher NL, Friedman N, Bolon DN, Rando OJ, Kaufman PD.
Elife. 2017 Sep 12;6. pii: e28836.

The Combined Effect of Oseltamivir and Favipiravir on Influenza A Virus Evolution.
Ormond L, Liu P, Matuszewski S, Renzette N, Bank C, Zeldovich K, Bolon DN, Kowalik TF, Finberg RW, Jensen JD, Wang JP.
Genome Biol Evol. 2017 Jul 1;9(7):1913-1924.

The diverse roles of Hsp90 and where to find them.
Van Oosten-Hawle P, Bolon DN, LaPointe P.
Nat Struct Mol Biol. 2017 Jan 5;24(1):1-4.

Molecular Basis for Differential Patterns of Drug Resistance in Influenza N1 and N2 Neuraminidase.
Prachanronarong KL, Özen A, Thayer KM, Yilmaz LS, Zeldovich KB, Bolon DN, Kowalik TF, Jensen JD, Finberg RW, Wang JP, Kurt-Yilmaz N, Schiffer CA.
J Chem Theory Comput. 2016 Dec 13;12(12):6098-6108.

An experimental evaluation of drug-induced mutational meltdown as an antiviral treatment strategy.
Bank C, Renzette N, Liu P, Matuszewski S, Shim H, Foll M, Bolon DN, Zeldovich KB, Kowalik TF, Finberg RW, Wang JP, Jensen JD.
Evolution. 2016 Nov;70(11):2470-2484.

Saturation Mutagenesis of the HIV-1 Envelope CD4 Binding Loop Reveals Residues Controlling Distinct Trimer Conformations.
Duenas-Decamp M, Jiang L, Bolon D, Clapham PR.
PLoS Pathog. 2016 Nov 7;12(11):e1005988.

Editorial.
Bolon DN, Baker D, Tawfik DS.
Protein Sci. 2016 Jul;25(7):1164-7.

Determination of ubiquitin fitness landscapes under different chemical stresses in a classroom setting.
Mavor D, Barlow K, Thompson S, Barad BA, Bonny AR, Cario CL, Gaskins G, Liu Z, Deming L, Axen SD, Caceres E, Chen W, Cuesta A, Gate RE, Green EM, Hulce KR, Ji W, Kenner LR, Mensa B, Morinishi LS, Moss SM, Mravic M, Muir RK, Niekamp S, Nnadi CI, Palovcak E, Poss EM, Ross TD, Salcedo EC, See SK, Subramaniam M, Wong AW, Li J, Thorn KS, Conchúir SÓ, Roscoe BP, Chow ED, DeRisi JL, Kortemme T, Bolon DN, Fraser JS.
Elife. 2016 Apr 25;5. pii: e15802.

Systematic Mutant Analyses Elucidate General and Client-Specific Aspects of Hsp90 Function.
Mishra P, Flynn JM, Starr TN, Bolon DNA.
Cell Rep. 2016 Apr 19;15(3):588-598.

Quantifying and understanding the fitness effects of protein mutations: Laboratory versus nature.
Boucher JI, Bolon DN, Tawfik DS.
Protein Sci. 2016 Jul;25(7):1219-26.

A Balance between Inhibitor Binding and Substrate Processing Confers Influenza Drug Resistance.
Jiang L, Liu P, Bank C, Renzette N, Prachanronarong K, Yilmaz LS, Caffrey DR, Zeldovich KB, Schiffer CA, Kowalik TF, Jensen JD, Finberg RW, Wang JP, Bolon DNA.
J Mol Biol. 2016 Feb 13;428(3):538-553.

Mechanistic Asymmetry in Hsp90 Dimers.
Flynn JM, Mishra P, Bolon DN.
J Mol Biol. 2015 Sep 11;427(18):2904-11.

Positive Selection Drives Preferred Segment Combinations during Influenza Virus Reassortment.
Zeldovich KB, Liu P, Renzette N, Foll M, Pham ST, Venev SV, Gallagher GR, Bolon DN, Kurt-Jones EA, Jensen JD, Caffrey DR, Schiffer CA, Kowalik TF, Wang JP, Finberg RW.
Mol Biol Evol. 2015 Jun;32(6):1519-32.

A systematic survey of an intragenic epistatic landscape.
Bank C, Hietpas RT, Jensen JD, Bolon DN.
Mol Biol Evol. 2015 Jan;32(1):229-38.

Viewing protein fitness landscapes through a next-gen lens.
Boucher JI, Cote P, Flynn J, Jiang L, Laban A, Mishra P, Roscoe BP, Bolon DN.
Genetics. 2014 Oct;198(2):461-71.

Systematic exploration of ubiquitin sequence, E1 activation efficiency, and experimental fitness in yeast.
Roscoe BP, Bolon DN.
J Mol Biol. 2014 Jul 29;426(15):2854-70.

Influenza virus drug resistance: a time-sampled population genetics perspective.
Foll M, Poh YP, Renzette N, Ferrer-Admetlla A, Bank C, Shim H, Malaspinas AS, Ewing G, Liu P, Wegmann D, Caffrey DR, Zeldovich KB, Bolon DN, Wang JP, Kowalik TF, Schiffer CA, Finberg RW, Jensen JD.
PLoS Genet. 2014 Feb 27;10(2):e1004185.

Designed Hsp90 heterodimers reveal an asymmetric ATPase-driven mechanism in vivo.
Mishra P, Bolon DN.
Mol Cell. 2014 Jan 23;53(2):344-50.

A bayesian MCMC approach to assess the complete distribution of fitness effects of new mutations: uncovering the potential for adaptive walks in challenging environments.
Bank C, Hietpas RT, Wong A, Bolon DN, Jensen JD.
Genetics. 2014 Mar;196(3):841-52.

Alanine scan of core positions in ubiquitin reveals links between dynamics, stability, and function.
Lee SY, Pullen L, Virgil DJ, Castañeda CA, Abeykoon D, Bolon DN, Fushman D.
J Mol Biol. 2014 Apr 3;426(7):1377-89.

Shifting fitness landscapes in response to altered environments.
Hietpas RT, Bank C, Jensen JD, Bolon DNA.
Evolution. 2013 Dec;67(12):3512-22.

Evolution of the influenza A virus genome during development of oseltamivir resistance in vitro.
Renzette N, Caffrey DR, Zeldovich KB, Liu P, Gallagher GR, Aiello D, Porter AJ, Kurt-Jones EA, Bolon DN, Poh YP, Jensen JD, Schiffer CA, Kowalik TF, Finberg RW, Wang JP.
J Virol. 2014 Jan;88(1):272-81.

Resistance to vemurafenib resulting from a novel mutation in the BRAFV600E kinase domain.
Wagenaar TR, Ma L, Roscoe B, Park SM, Bolon DN, Green MR.
Pigment Cell Melanoma Res. 2014 Jan;27(1):124-33.

Posttranslational modification and conformational state of heat shock protein 90 differentially affect binding of chemically diverse small molecule inhibitors.
Beebe K, Mollapour M, Scroggins B, Prodromou C, Xu W, Tokita M, Taldone T, Pullen L, Zierer BK, Lee MJ, Trepel J, Buchner J, Bolon D, Chiosis G, Neckers L.
Oncotarget. 2013 Jul;4(7):1065-74.

Latent effects of Hsp90 mutants revealed at reduced expression levels.
Jiang L, Mishra P, Hietpas RT, Zeldovich KB, Bolon DN.
PLoS Genet. 2013 Jun;9(6):e1003600.

Analyses of the effects of all ubiquitin point mutants on yeast growth rate.
Roscoe BP, Thayer KM, Zeldovich KB, Fushman D, Bolon DN.
J Mol Biol. 2013 Apr 26;425(8):1363-77.

Fitness analyses of all possible point mutations for regions of genes in yeast.
Hietpas R, Roscoe B, Jiang L, Bolon DN.
Nat Protoc. 2012 Jun 21;7(7):1382-96.

Solubility-promoting function of Hsp90 contributes to client maturation and robust cell growth.
Pursell NW, Mishra P, Bolon DN.
Eukaryot Cell. 2012 Aug;11(8):1033-41.

Hydrophobic core flexibility modulates enzyme activity in HIV-1 protease.
Mittal S, Cai Y, Nalam MN, Bolon DN, Schiffer CA.
J Am Chem Soc. 2012 Mar 7;134(9):4163-8.

Bound for observation.
Bolon DN.
J Mol Biol. 2012 Jan 6;415(1):1-2.

Hsp90 and client protein maturation.
Wayne N, Mishra P, Bolon DN.
Methods Mol Biol. 2011;787:33-44.

Experimental illumination of a fitness landscape.
Hietpas RT, Jensen JD, Bolon DN.
Proc Natl Acad Sci U S A. 2011 May 10;108(19):7896-901.

Enforced N-domain proximity stimulates Hsp90 ATPase activity and is compatible with function in vivo.
Pullen L, Bolon DN.
J Biol Chem. 2011 Apr 1;286(13):11091-8.

Charge-rich regions modulate the anti-aggregation activity of Hsp90.
Wayne N, Bolon DN.
J Mol Biol. 2010 Sep 3;401(5):931-9.

Modular control of cross-oligomerization: analysis of superstabilized Hsp90 homodimers in vivo.
Wayne N, Lai Y, Pullen L, Bolon DN.
J Biol Chem. 2010 Jan 1;285(1):234-41.

Watching proteins in motion.
Munson M, Bolon DN.
Genome Biol. 2009;10(10):316.

Mutations in the hydrophobic core of ubiquitin differentially affect its recognition by receptor proteins.
Haririnia A, Verma R, Purohit N, Twarog MZ, Deshaies RJ, Bolon D, Fushman D.
J Mol Biol. 2008 Jan 25;375(4):979-96. Epub 2007 Nov 13.

Dimerization of Hsp90 is required for in vivo function. Design and analysis of monomers and dimers.
Wayne N, Bolon DN.
J Biol Chem. 2007 Nov 30;282(48):35386-95.

Altered tethering of the SspB adaptor to the ClpXP protease causes changes in substrate delivery.
McGinness KE, Bolon DN, Kaganovich M, Baker TA, Sauer RT.
J Biol Chem. 2007 Apr 13;282(15):11465-73.

Specificity versus stability in computational protein design.
Bolon DN, Grant RA, Baker TA, Sauer RT.
Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12724-9.

Asymmetric interactions of ATP with the AAA+ ClpX6 unfoldase: allosteric control of a protein machine.
Hersch GL, Burton RE, Bolon DN, Baker TA, Sauer RT.
Cell. 2005 Jul 1;121(7):1017-27.

Nucleotide-dependent substrate handoff from the SspB adaptor to the AAA+ ClpXP protease.
Bolon DN, Grant RA, Baker TA, Sauer RT.
Mol Cell. 2004 Nov 5;16(3):343-50.

Sculpting the proteome with AAA(+) proteases and disassembly machines.
Sauer RT, Bolon DN, Burton BM, Burton RE, Flynn JM, Grant RA, Hersch GL, Joshi SA, Kenniston JA, Levchenko I, Neher SB, Oakes ES, Siddiqui SM, Wah DA, Baker TA.
Cell. 2004 Oct 1;119(1):9-18. Review.

Bivalent tethering of SspB to ClpXP is required for efficient substrate delivery: a protein-design study.
Bolon DN, Wah DA, Hersch GL, Baker TA, Sauer RT.
Mol Cell. 2004 Feb 13;13(3):443-9.

Flexible linkers leash the substrate binding domain of SspB to a peptide module that stabilizes delivery complexes with the AAA+ ClpXP protease.
Wah DA, Levchenko I, Rieckhof GE, Bolon DN, Baker TA, Sauer RT.
Mol Cell. 2003 Aug;12(2):355-63.

Prudent modeling of core polar residues in computational protein design.
Bolon DN, Marcus JS, Ross SA, Mayo SL.
J Mol Biol. 2003 Jun 6;329(3):611-22.

De novo design of biocatalysts.
Bolon DN, Voigt CA, Mayo SL.
Curr Opin Chem Biol. 2002 Apr;6(2):125-9. Review.

Enzyme-like proteins by computational design.
Bolon DN, Mayo SL.
Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14274-9.

Polar residues in the protein core of Escherichia coli thioredoxin are important for fold specificity.
Bolon DN, Mayo SL.
Biochemistry. 2001 Aug 28;40(34):10047-53.