James Fraser, PhD

Department Chair and Professor

Bioengineering

+1 415 493-8421

The long-term goals of our research are to understand how protein conformational ensembles are reshaped by perturbations, such as mutation and ligand binding, and to quantify how these perturbations impact protein function and organismal fitness. To accomplish these goals, we create new computational and biophysical approaches to study how proteins move between different conformational states. As a graduate student, with Tom Alber at UC Berkeley, James established room temperature X-ray data collection techniques and electron density sampling strategies to define protein conformational ensembles essential for catalysis. Prior to starting an independent position at UCSF, he was a visiting EMBO Short Term Fellow in the lab of Dan Tawfik at the Weizmann Institute of Science in Israel and developed expertise in directed evolution and high-throughput assays of enzymatic or binding activity. In 2011, James started his independent research career as a QB3 at UCSF Fellow and in 2013 was appointed as an Assistant Professor of Bioengineering and Therapeutic Sciences. At UCSF, his lab continue to pioneer new methods for extracting the maximal information from X-ray diffraction experiments and electron density maps. Additionally, the group uses two complementary approaches to study the relationship between protein conformational ensembles and function. To dissect consequences of mutations on organismal fitness, we use high-throughput systems biology and biophysical methods to analyze large sets of clinically or biophysically interesting mutations. To improve our ability to engineer new protein functions, we investigate changes to the conformational ensemble as new enzymatic and binding functions emerge from directed evolution studies.

Publications:

Structural characterization of ligand binding and pH-specific enzymatic activity of mouse Acidic Mammalian Chitinase.

bioRxiv : the preprint server for biology

Díaz RE, Ecker AK, Correy GJ, Asthana P, Young ID, Faust B, Thompson MC, Seiple IB, Van Dyken SJ, Locksley RM, Fraser JS

Recommendations for accelerating open preprint peer review to improve the culture of science.

PLoS biology

Avissar-Whiting M, Belliard F, Bertozzi SM, Brand A, Brown K, Clément-Stoneham G, Dawson S, Dey G, Ecer D, Edmunds SC, Farley A, Fischer TD, Franko M, Fraser JS, Funk K, Ganier C, Harrison M, Hatch A, Hazlett H, Hindle S, Hook DW, Hurst P, Kamoun S, Kiley R, Lacy MM, LaFlamme M, Lawrence R, Lemberger T, Leptin M, Lumb E, MacCallum CJ, Marcum CS, Marinello G, Mendonça A, Monaco S, Neves K, Pattinson D, Polka JK, Puebla I, Rittman M, Royle SJ, Saderi D, Sever R, Shearer K, Spiro JE, Stern B, Taraborelli D, Vale R, Vasquez CG, Waltman L, Watt FM, Weinberg ZY, Williams M

Discovery and clinical proof-of-concept of RLY-2608, a first-in-class mutant-selective allosteric PI3Ka inhibitor that decouples anti-tumor activity from hyperinsulinemia.

Cancer discovery

Varkaris A, Pazolli E, Gunaydin H, Wang Q, Pierce L, Boezio AA, DiPietro L, Frost A, Giordanetto F, Hamilton EP, Harris K, Holliday M, Hunter TL, Iskandar A, Ji Y, Larivée A, LaRochelle JR, Lescarbeau A, Llambi F, Lormil B, Mader MM, Mar BG, Martin I, McLean TH, Michelsen K, Pechersky Y, Puente-Poushnejad E, Samadani R, Schram AM, Shortsleeves K, Swaminathan S, Tajmir S, Tan G, Tang Y, Valverde R, Wehrenberg B, Wilbur J, Williams BR, Zeng H, Walters WP, Wolf BB, Shaw DE, Bergstrom DA, Watters J, Fraser JS, Fortin PD, Kipp DR

Computing a Bayesian multi-state model of a protein structure from an X-ray diffraction pattern.

Biophysical journal

Matthew P. Hancock, James S. Fraser, Andrej Sali

Extracting conformational heterogeneity from 2D and 3D cryo-EM data.

Biophysical journal

Samuel Hoff, Massimiliano Bonomi, James Fraser, Eric Greene

Product-stabilized filamentation by human glutamine synthetase allosterically tunes activity.

Biophysical journal

Eric R. Greene, Richard Muniz, Hiroki Yamamura, Samuel Hoff, Angelika Arada, Priyanka Bajaj, Daphne Chen, John D. Lee, Massimiliano Bonomi, Justin M. Kollman, James Fraser

Role of conformational dynamics in the catalytic mechanism of viral macrodomains.

Biophysical journal

Rishav Mitra, James Fraser

Structure is beauty, but not always truth.

Cell

Fraser JS, Murcko MA

MET variants with activating N-lobe mutations identified in hereditary papillary renal cell carcinomas still require ligand stimulation.

bioRxiv : the preprint server for biology

Guérin C, Vinchent A, Fernandes M, Damour I, Laratte A, Tellier R, Estevam GO, Meneboo JP, Villenet C, Descarpentries C, Fraser JS, Figeac M, Cortot AB, Rouleau E, Tulasne D

Mapping protein dynamics at high spatial resolution with temperature-jump X-ray crystallography.

Nature chemistry

Wolff AM, Nango E, Young ID, Brewster AS, Kubo M, Nomura T, Sugahara M, Owada S, Barad BA, Ito K, Bhowmick A, Carbajo S, Hino T, Holton JM, Im D, O'Riordan LJ, Tanaka T, Tanaka R, Sierra RG, Yumoto F, Tono K, Iwata S, Sauter NK, Fraser JS, Thompson MC

A type 2 immune circuit in the stomach controls mammalian adaptation to dietary chitin.

Science (New York, N.Y.)

Kim DH, Wang Y, Jung H, Field RL, Zhang X, Liu TC, Ma C, Fraser JS, Brestoff JR, Van Dyken SJ

A single inactivating amino acid change in the SARS-CoV-2 NSP3 Mac1 domain attenuates viral replication in vivo.

PLoS pathogens

Taha TY, Suryawanshi RK, Chen IP, Correy GJ, McCavitt-Malvido M, O'Leary PC, Jogalekar MP, Diolaiti ME, Kimmerly GR, Tsou CL, Gascon R, Montano M, Martinez-Sobrido L, Krogan NJ, Ashworth A, Fraser JS, Ott M

Chemoenzymatic Syntheses of Fluorine-18-Labeled Disaccharides from [18F] FDG Yield Potent Sensors of Living Bacteria In Vivo.

Journal of the American Chemical Society

Sorlin AM, López-Álvarez M, Rabbitt SJ, Alanizi AA, Shuere R, Bobba KN, Blecha J, Sakhamuri S, Evans MJ, Bayles KW, Flavell RR, Rosenberg OS, Sriram R, Desmet T, Nidetzky B, Engel J, Ohliger MA, Fraser JS, Wilson DM

Conserved regulatory motifs in the juxtamembrane domain and kinase N-lobe revealed through deep mutational scanning of the MET receptor tyrosine kinase domain.

bioRxiv : the preprint server for biology

Estevam GO, Linossi EM, Macdonald CB, Espinoza CA, Michaud JM, Coyote-Maestas W, Collisson EA, Jura N, Fraser JS

Refinement of multiconformer ensemble models from multi-temperature X-ray diffraction data.

Methods in enzymology

Du S, Wankowicz SA, Yabukarski F, Doukov T, Herschlag D, Fraser JS

Uncovering Protein Ensembles: Automated Multiconformer Model Building for X-ray Crystallography and Cryo-EM.

bioRxiv : the preprint server for biology

Wankowicz SA, Ravikumar A, Sharma S, Riley BT, Raju A, Hogan DW, van den Bedem H, Keedy DA, Fraser JS

Chemoenzymatic syntheses of fluorine-18-labeled disaccharides from [ 18 F]FDG yield potent sensors of living bacteria in vivo.

bioRxiv : the preprint server for biology

A single inactivating amino acid change in the SARS-CoV-2 NSP3 Mac1 domain attenuates viral replication and pathogenesis in vivo.

bioRxiv : the preprint server for biology

Taha TY, Suryawanshi RK, Chen IP, Correy GJ, O'Leary PC, Jogalekar MP, McCavitt-Malvido M, Diolaiti M, Kimmerly GR, Tsou CL, Sobrido LM, Krogan NJ, Ashworth A, Fraser JS, Ott M

Refinement of Multiconformer Ensemble Models from Multi-temperature X-ray Diffraction Data.

bioRxiv : the preprint server for biology

Du S, Wankowicz SA, Yabukarski F, Doukov T, Herschlag D, Fraser JS

Molecular evidence of widespread benzimidazole drug resistance in Ancylostoma caninum from domestic dogs throughout the USA and discovery of a novel �-tubulin benzimidazole resistance mutation.

PLoS pathogens

Venkatesan A, Jimenez Castro PD, Morosetti A, Horvath H, Chen R, Redman E, Dunn K, Collins JB, Fraser JS, Anderson EC, Kaplan RM, Gilleard JS

DIMPLE: deep insertion, deletion, and missense mutation libraries for exploring protein variation in evolution, disease, and biology.

Genome biology

Macdonald CB, Nedrud D, Grimes PR, Trinidad D, Fraser JS, Coyote-Maestas W

Bacteriophages inhibit and evade cGAS-like immune function in bacteria.

Cell

Huiting E, Cao X, Ren J, Athukoralage JS, Luo Z, Silas S, An N, Carion H, Zhou Y, Fraser JS, Feng Y, Bondy-Denomy J

Context-specific inhibition of translation in mycobacterium.

Biophysical journal

Mohamad T. Dandan, James S. Fraser

Reaction coordinate dependent fibrillar formation of human glutamine synthetase tunes activity.

Biophysical journal

Eric R. Greene, Richard Muniz, Angelika Arada, D. John Lee, Daphne Chen, Erin Thompson, Hiroki Yamamura, Justin M. Kollman, James Fraser

Large language models generate functional protein sequences across diverse families.

Nature biotechnology

Madani A, Krause B, Greene ER, Subramanian S, Mohr BP, Holton JM, Olmos JL, Xiong C, Sun ZZ, Socher R, Fraser JS, Naik N

Iterative computational design and crystallographic screening identifies potent inhibitors targeting the Nsp3 macrodomain of SARS-CoV-2.

Proceedings of the National Academy of Sciences of the United States of America

Gahbauer S, Correy GJ, Schuller M, Ferla MP, Doruk YU, Rachman M, Wu T, Diolaiti M, Wang S, Neitz RJ, Fearon D, Radchenko DS, Moroz YS, Irwin JJ, Renslo AR, Taylor JC, Gestwicki JE, von Delft F, Ashworth A, Ahel I, Shoichet BK, Fraser JS

Molecular-dynamics simulation methods for macromolecular crystallography.

Acta crystallographica. Section D, Structural biology

Wych DC, Aoto PC, Vu L, Wolff AM, Mobley DL, Fraser JS, Taylor SS, Wall ME

A language model beats alphafold2 on orphans.

Nature biotechnology

Michaud JM, Madani A, Fraser JS

Ensemble-function relationships to dissect mechanisms of enzyme catalysis.

Science advances

Yabukarski F, Doukov T, Pinney MM, Biel JT, Fraser JS, Herschlag D

Of problems and opportunities-How to treat and how to not treat crystallographic fragment screening data.

Protein science : a publication of the Protein Society

Weiss MS, Wollenhaupt J, Correy GJ, Fraser JS, Heine A, Klebe G, Krojer T, Thunissen M, Pearce NM

Innate type 2 immunity controls hair follicle commensalism by Demodex mites.

Immunity

Ricardo-Gonzalez RR, Kotas ME, O'Leary CE, Singh K, Damsky W, Liao C, Arouge E, Tenvooren I, Marquez DM, Schroeder AW, Cohen JN, Fassett MS, Lee J, Daniel SG, Bittinger K, Díaz RE, Fraser JS, Ali N, Ansel KM, Spitzer MH, Liang HE, Locksley RM

The mechanisms of catalysis and ligand binding for the SARS-CoV-2 NSP3 macrodomain from neutron and x-ray diffraction at room temperature.

Science advances

Correy GJ, Kneller DW, Phillips G, Pant S, Russi S, Cohen AE, Meigs G, Holton JM, Gahbauer S, Thompson MC, Ashworth A, Coates L, Kovalevsky A, Meilleur F, Fraser JS

Innate type 2 immunity controls hair follicle commensalism by Demodex mites.

The Journal of Immunology

Roberto R Ricardo-Gonzalez, Maya E Kotas, Claire O’Leary, Iliana Tenvooren, Diana Marquez, Katelyn Singh, William Damsky, Chang Liao, Andrew Schroeder, Jarish Cohen, Marlys S Fassett, Jinwoo Lee, Scott G Daniel, Kyle Bittinger, Roberto Efrain Diaz, James Fraser, Karl Mark Ansel, Matthew Spitzer, Hong-Erh Liang, Richard M Locksley

Ligand binding remodels protein side chain conformational heterogeneity.

eLife

Wankowicz SA, de Oliveira SH, Hogan DW, van den Bedem H, Fraser JS

Accurate positioning of functional residues with robotics-inspired computational protein design.

Proceedings of the National Academy of Sciences of the United States of America

Krivacic C, Kundert K, Pan X, Pache RA, Liu L, Conchúir SO, Jeliazkov JR, Gray JJ, Thompson MC, Fraser JS, Kortemme T

Structural basis for context-specific inhibition of translation by oxazolidinone antibiotics.

Nature structural & molecular biology

Tsai K, Stojkovic V, Lee DJ, Young ID, Szal T, Klepacki D, Vázquez-Laslop N, Mankin AS, Fraser JS, Fujimori DG

Integration of software tools for integrative modeling of biomolecular systems.

Journal of structural biology

Hancock M, Peulen TO, Webb B, Poon B, Fraser JS, Adams P, Sali A

Directed evolution of the rRNA methylating enzyme Cfr reveals molecular basis of antibiotic resistance.

eLife

Tsai K, Stojkovic V, Noda-Garcia L, Young ID, Myasnikov AG, Kleinman J, Palla A, Floor SN, Frost A, Fraser JS, Tawfik DS, Fujimori DG

A counter-enzyme complex regulates glutamate metabolism in Bacillus subtilis.

Nature chemical biology

Jayaraman V, Lee DJ, Elad N, Vimer S, Sharon M, Fraser JS, Tawfik DS

CryoEM and AI reveal a structure of SARS-CoV-2 Nsp2, a multifunctional protein involved in key host processes.

Research square

Verba K, Gupta M, Azumaya C, Moritz M, Pourmal S, Diallo A, Merz G, Jang G, Bouhaddou M, Fossati A, Brilot A, Diwanji D, Hernandez E, Herrera N, Kratochvil H, Lam V, Li F, Li Y, Nguyen H, Nowotny C, Owens T, Peters J, Rizo A, Schulze-Gahmen U, Smith A, Young I, Yu Z, Asarnow D, Billesbølle C, Campbell M, Chen J, Chen KH, Chio US, Dickinson M, Doan L, Jin M, Kim K, Li J, Li YL, Linossi E, Liu Y, Lo M, Lopez J, Lopez K, Mancino A, Iii FM, Paul M, Pawar K, Pelin A, Pospiech T, Puchades C, Remesh S, Safari M, Schaefer K, Sun M, Tabios M, Thwin A, Titus E, Trenker R, Tse E, Tsui TKM, Feng F, Zhang K, Zhang Y, Zhao J, Zhou F, Zhou Y, Zuliani-Alvarez L, Agard D, Cheng Y, Fraser J, Jura N, Kortemme T, Manglik A, Southworth D, Stroud R, Swaney D, Krogan N, Frost A, Rosenberg O

State of the structure address on MET receptor activation by HGF.

Biochemical Society transactions

ORACLE reveals a bright future to fight bacteria.

eLife

Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking.

Science advances

Cryo-EM model validation recommendations based on outcomes of the 2019 EMDataResource challenge.

Nature methods

Lawson CL, Kryshtafovych A, Adams PD, Afonine PV, Baker ML, Barad BA, Bond P, Burnley T, Cao R, Cheng J, Chojnowski G, Cowtan K, Dill KA, DiMaio F, Farrell DP, Fraser JS, Herzik MA, Hoh SW, Hou J, Hung LW, Igaev M, Joseph AP, Kihara D, Kumar D, Mittal S, Monastyrskyy B, Olek M, Palmer CM, Patwardhan A, Perez A, Pfab J, Pintilie GD, Richardson JS, Rosenthal PB, Sarkar D, Schäfer LU, Schmid MF, Schröder GF, Shekhar M, Si D, Singharoy A, Terashi G, Terwilliger TC, Vaiana A, Wang L, Wang Z, Wankowicz SA, Williams CJ, Winn M, Wu T, Yu X, Zhang K, Berman HM, Chiu W

Assessment of enzyme active site positioning and tests of catalytic mechanisms through X-ray-derived conformational ensembles.

Proceedings of the National Academy of Sciences of the United States of America

Yabukarski F, Biel JT, Pinney MM, Doukov T, Powers AS, Fraser JS, Herschlag D

Genetic interaction mapping informs integrative structure determination of protein complexes.

Science (New York, N.Y.)

Braberg H, Echeverria I, Bohn S, Cimermancic P, Shiver A, Alexander R, Xu J, Shales M, Dronamraju R, Jiang S, Dwivedi G, Bogdanoff D, Chaung KK, Hüttenhain R, Wang S, Mavor D, Pellarin R, Schneidman D, Bader JS, Fraser JS, Morris J, Haber JE, Strahl BD, Gross CA, Dai J, Boeke JD, Sali A, Krogan NJ

qFit 3: Protein and ligand multiconformer modeling for X-ray crystallographic and single-particle cryo-EM density maps.

Protein science : a publication of the Protein Society

Riley BT, Wankowicz SA, de Oliveira SHP, van Zundert GCP, Hogan DW, Fraser JS, Keedy DA, van den Bedem H

Discovery of allosteric binding sites by crystallographic fragment screening.

Current opinion in structural biology

Krojer T, Fraser JS, von Delft F

DNA-binding proteins meet their mismatch.

Nature

Kundert K, Fraser JS

Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms.

Science (New York, N.Y.)

Gordon DE, Hiatt J, Bouhaddou M, Rezelj VV, Ulferts S, Braberg H, Jureka AS, Obernier K, Guo JZ, Batra J, Kaake RM, Weckstein AR, Owens TW, Gupta M, Pourmal S, Titus EW, Cakir M, Soucheray M, McGregor M, Cakir Z, Jang G, O'Meara MJ, Tummino TA, Zhang Z, Foussard H, Rojc A, Zhou Y, Kuchenov D, Hüttenhain R, Xu J, Eckhardt M, Swaney DL, Fabius JM, Ummadi M, Tutuncuoglu B, Rathore U, Modak M, Haas P, Haas KM, Naing ZZC, Pulido EH, Shi Y, Barrio-Hernandez I, Memon D, Petsalaki E, Dunham A, Marrero MC, Burke D, Koh C, Vallet T, Silvas JA, Azumaya CM, Billesbølle C, Brilot AF, Campbell MG, Diallo A, Dickinson MS, Diwanji D, Herrera N, Hoppe N, Kratochvil HT, Liu Y, Merz GE, Moritz M, Nguyen HC, Nowotny C, Puchades C, Rizo AN, Schulze-Gahmen U, Smith AM, Sun M, Young ID, Zhao J, Asarnow D, Biel J, Bowen A, Braxton JR, Chen J, Chio CM, Chio US, Deshpande I, Doan L, Faust B, Flores S, Jin M, Kim K, Lam VL, Li F, Li J, Li YL, Li Y, Liu X, Lo M, Lopez KE, Melo AA, Moss FR, Nguyen P, Paulino J, Pawar KI, Peters JK, Pospiech TH, Safari M, Sangwan S, Schaefer K, Thomas PV, Thwin AC, Trenker R, Tse E, Tsui TKM, Wang F, Whitis N, Yu Z, Zhang K, Zhang Y, Zhou F, Saltzberg D

Ensemble-based enzyme design can recapitulate the effects of laboratory directed evolution in silico.

Nature communications

Broom A, Rakotoharisoa RV, Thompson MC, Zarifi N, Nguyen E, Mukhametzhanov N, Liu L, Fraser JS, Chica RA

Synthetic group A streptogramin antibiotics that overcome Vat resistance.

Nature

Li Q, Pellegrino J, Lee DJ, Tran AA, Chaires HA, Wang R, Park JE, Ji K, Chow D, Zhang N, Brilot AF, Biel JT, van Zundert G, Borrelli K, Shinabarger D, Wolfe C, Murray B, Jacobson MP, Mühle E, Chesneau O, Fraser JS, Seiple IB

Expanding the space of protein geometries by computational design of de novo fold families.

Science (New York, N.Y.)

Pan X, Thompson MC, Zhang Y, Liu L, Fraser JS, Kelly MJS, Kortemme T

A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.

Nature

Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL, Tummino TA, Huettenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGregor MJ, Li Q, Meyer B, Roesch F, Vallet T, Mac Kain A, Miorin L, Moreno E, Naing ZZC, Zhou Y, Peng S, Shi Y, Zhang Z, Shen W, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Lyu J, Mathy CJP, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Rakesh R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Liboy-Lugo J, Lin Y, Huang XP, Liu Y, Wankowicz SA, Bohn M, Safari M, Ugur FS, Koh C, Savar NS, Tran QD, Shengjuler D, Fletcher SJ, O'Neal MC, Cai Y, Chang JCJ, Broadhurst DJ, Klippsten S, Sharp PP, Wenzell NA, Kuzuoglu D, Wang HY, Trenker R, Young JM, Cavero DA, Hiatt J, Roth TL, Rathore U, Subramanian A, Noack J, Hubert M, Stroud RM, Frankel AD, Rosenberg OS, Verba KA, Agard DA, Ott M, Emerman M, Jura N, von Zastrow M, Verdin E, Ashworth A, Schwartz O, d'Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor SN, Fraser JS, Gross JD, Sali A, Roth BL, Ruggero D, Taunton J, Kortemme T, Beltrao P, Vignuzzi M, García-Sastre A, Shokat KM, Shoichet BK, Krogan NJ

Assessment of the nucleotide modifications in the high-resolution cryo-electron microscopy structure of the Escherichia coli 50S subunit.

Nucleic acids research

Stojkovic V, Myasnikov AG, Young ID, Frost A, Fraser JS, Fujimori DG

Comparing serial X-ray crystallography and microcrystal electron diffraction (MicroED) as methods for routine structure determination from small macromolecular crystals.

IUCrJ

Wolff AM, Young ID, Sierra RG, Brewster AS, Martynowycz MW, Nango E, Sugahara M, Nakane T, Ito K, Aquila A, Bhowmick A, Biel JT, Carbajo S, Cohen AE, Cortez S, Gonzalez A, Hino T, Im D, Koralek JD, Kubo M, Lazarou TS, Nomura T, Owada S, Samelson AJ, Tanaka T, Tanaka R, Thompson EM, van den Bedem H, Woldeyes RA, Yumoto F, Zhao W, Tono K, Boutet S, Iwata S, Gonen T, Sauter NK, Fraser JS, Thompson MC

What Will Computational Modeling Approaches Have to Say in the Era of Atomistic Cryo-EM Data?

Journal of chemical information and modeling

Fraser JS, Lindorff-Larsen K, Bonomi M

Differences in the chitinolytic activity of mammalian chitinases on soluble and insoluble substrates.

Protein science : a publication of the Protein Society

Barad BA, Liu L, Diaz RE, Basilio R, Van Dyken SJ, Locksley RM, Fraser JS

Liquid-like and rigid-body motions in molecular-dynamics simulations of a crystalline protein.

Structural dynamics (Melville, N.Y.)

Wych DC, Fraser JS, Mobley DL, Wall ME

Mix-and-inject XFEL crystallography reveals gated conformational dynamics during enzyme catalysis.

Proceedings of the National Academy of Sciences of the United States of America

Dasgupta M, Budday D, de Oliveira SHP, Madzelan P, Marchany-Rivera D, Seravalli J, Hayes B, Sierra RG, Boutet S, Hunter MS, Alonso-Mori R, Batyuk A, Wierman J, Lyubimov A, Brewster AS, Sauter NK, Applegate GA, Tiwari VK, Berkowitz DB, Thompson MC, Cohen AE, Fraser JS, Wall ME, van den Bedem H, Wilson MA

Computational design of a modular protein sense-response system.

Science (New York, N.Y.)

Glasgow AA, Huang YM, Mandell DJ, Thompson M, Ritterson R, Loshbaugh AL, Pellegrino J, Krivacic C, Pache RA, Barlow KA, Ollikainen N, Jeon D, Kelly MJS, Fraser JS, Kortemme T

Co-occurring alterations in the RAS-MAPK pathway limit response to MET inhibitor treatment in MET exon 14 skipping mutation-positive lung cancer.

Clinical cancer research : an official journal of the American Association for Cancer Research

Rotow JK, Gui P, Wu W, Raymond VM, Lanman RB, Kaye FJ, Peled N, Fece de la Cruz F, Nadres B, Corcoran RB, Yeh I, Bastian BC, Starostik P, Newsom K, Olivas V, Wolff AM, Fraser JS, Collisson EA, McCoach CE, Camidge DR, Pacheco J, Bazhenova L, Li T, Bivona TG, Blakely CM

Temperature-jump solution X-ray scattering reveals distinct motions in a dynamic enzyme.

Nature chemistry

Thompson MC, Barad BA, Wolff AM, Sun Cho H, Schotte F, Schwarz DMC, Anfinrud P, Fraser JS

Synthetic Essentiality of Metabolic Regulator PDHK1 in PTEN-Deficient Cells and Cancers.

Cell reports

Chatterjee N, Pazarentzos E, Mayekar MK, Gui P, Allegakoen DV, Hrustanovic G, Olivas V, Lin L, Verschueren E, Johnson JR, Hofree M, Yan JJ, Newton BW, Dollen JV, Earnshaw CH, Flanagan J, Chan E, Asthana S, Ideker T, Wu W, Suzuki J, Barad BA, Kirichok Y, Fraser JS, Weiss WA, Krogan NJ, Tulpule A, Sabnis AJ, Bivona TG

Promoting transparency and reproducibility in enhanced molecular simulations.

Nature methods

Biomaterials in non-integer dimensions.

Nature chemistry

Young ID, Fraser JS

Effects of a-tubulin acetylation on microtubule structure and stability.

Proceedings of the National Academy of Sciences of the United States of America

Eshun-Wilson L, Zhang R, Portran D, Nachury MV, Toso DB, Löhr T, Vendruscolo M, Bonomi M, Fraser JS, Nogales E

Biophysical Characterization of a Disabled Double Mutant of Soybean Lipoxygenase: The "Undoing" of Precise Substrate Positioning Relative to Metal Cofactor and an Identified Dynamical Network.

Journal of the American Chemical Society

Hu S, Offenbacher AR, Thompson EM, Gee CL, Wilcoxen J, Carr CAM, Prigozhin DM, Yang V, Alber T, Britt RD, Fraser JS, Klinman JP

qFit-ligand reveals widespread conformational heterogeneity of drug-like molecules in X-ray electron density maps.

Journal of medicinal chemistry

van Zundert G, Hudson BM, de Oliveira S, Keedy DA, Fonseca R, Heliou A, Suresh P, Borrelli K, Day T, Fraser J, van den Bedem H

A Multi-model Approach to Assessing Local and Global Cryo-EM Map Quality.

Structure (London, England : 1993)

Herzik MA, Fraser JS, Lander GC

Together scientists and journalists can spot poor preprints.

Nature

Fraser J, Polka J

Extending chemical perturbations of the ubiquitin fitness landscape in a classroom setting reveals new constraints on sequence tolerance.

Biology open

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

An expanded allosteric network in PTP1B by multitemperature crystallography, fragment screening, and covalent tethering.

eLife

Keedy DA, Hill ZB, Biel JT, Kang E, Rettenmaier TJ, Brandao-Neto J, Pearce NM, von Delft F, Wells JA, Fraser JS

Rescue of conformational dynamics in enzyme catalysis by directed evolution.

Nature communications

Otten R, Liu L, Kenner LR, Clarkson MW, Mavor D, Tawfik DS, Kern D, Fraser JS

Bringing diffuse X-ray scattering into focus.

Current opinion in structural biology

Wall ME, Wolff AM, Fraser JS

XFEL structures of the influenza M2 proton channel: Room temperature water networks and insights into proton conduction.

Proceedings of the National Academy of Sciences of the United States of America

Thomaston JL, Woldeyes RA, Nakane T, Yamashita A, Tanaka T, Koiwai K, Brewster AS, Barad BA, Chen Y, Lemmin T, Uervirojnangkoorn M, Arima T, Kobayashi J, Masuda T, Suzuki M, Sugahara M, Sauter NK, Tanaka R, Nureki O, Tono K, Joti Y, Nango E, Iwata S, Yumoto F, Fraser JS, DeGrado WF

Allosteric Inhibitors, Crystallography, and Comparative Analysis Reveal Network of Coordinated Movement across Human Herpesvirus Proteases.

Journal of the American Chemical Society

Acker TM, Gable JE, Bohn MF, Jaishankar P, Thompson MC, Fraser JS, Renslo AR, Craik CS

Hydrogen-Deuterium Exchange of Lipoxygenase Uncovers a Relationship between Distal, Solvent Exposed Protein Motions and the Thermal Activation Barrier for Catalytic Proton-Coupled Electron Tunneling.

ACS central science

Offenbacher AR, Hu S, Poss EM, Carr CAM, Scouras AD, Prigozhin DM, Iavarone AT, Palla A, Alber T, Fraser JS, Klinman JP

Flexibility and Design: Conformational Heterogeneity along the Evolutionary Trajectory of a Redesigned Ubiquitin.

Structure (London, England : 1993)

Biel JT, Thompson MC, Cunningham CN, Corn JE, Fraser JS

Cytidine deaminase efficiency of the lentiviral viral restriction factor APOBEC3C correlates with dimerization.

Nucleic acids research

Adolph MB, Ara A, Feng Y, Wittkopp CJ, Emerman M, Fraser JS, Chelico L

Conformational variation of proteins at room temperature is not dominated by radiation damage.

Journal of synchrotron radiation

Russi S, González A, Kenner LR, Keedy DA, Fraser JS, van den Bedem H

Automated structure refinement of macromolecular assemblies from cryo-EM maps using Rosetta.

eLife

Wang RY, Song Y, Barad BA, Cheng Y, Fraser JS, DiMaio F

From deep TLS validation to ensembles of atomic models built from elemental motions. Addenda and corrigendum.

Acta crystallographica. Section D, Structural biology

Urzhumtsev A, Afonine PV, Van Benschoten AH, Fraser JS, Adams PD

SCIENTIFIC COMMUNITY. Preprints for the life sciences.

Science (New York, N.Y.)

Berg JM, Bhalla N, Bourne PE, Chalfie M, Drubin DG, Fraser JS, Greider CW, Hendricks M, Jones C, Kiley R, King S, Kirschner MW, Krumholz HM, Lehmann R, Leptin M, Pulverer B, Rosenzweig B, Spiro JE, Stebbins M, Strasser C, Swaminathan S, Turner P, Vale RD, VijayRaghavan K, Wolberger C

Determination of ubiquitin fitness landscapes under different chemical stresses in a classroom setting.

eLife

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

Measuring and modeling diffuse scattering in protein X-ray crystallography.

Proceedings of the National Academy of Sciences of the United States of America

Van Benschoten AH, Liu L, Gonzalez A, Brewster AS, Sauter NK, Fraser JS, Wall ME

Data publication with the structural biology data grid supports live analysis.

Nature communications

Meyer PA, Socias S, Key J, Ransey E, Tjon EC, Buschiazzo A, Lei M, Botka C, Withrow J, Neau D, Rajashankar K, Anderson KS, Baxter RH, Blacklow SC, Boggon TJ, Bonvin AM, Borek D, Brett TJ, Caflisch A, Chang CI, Chazin WJ, Corbett KD, Cosgrove MS, Crosson S, Dhe-Paganon S, Di Cera E, Drennan CL, Eck MJ, Eichman BF, Fan QR, Ferré-D'Amaré AR, Fromme JC, Garcia KC, Gaudet R, Gong P, Harrison SC, Heldwein EE, Jia Z, Keenan RJ, Kruse AC, Kvansakul M, McLellan JS, Modis Y, Nam Y, Otwinowski Z, Pai EF, Pereira PJ, Petosa C, Raman CS, Rapoport TA, Roll-Mecak A, Rosen MK, Rudenko G, Schlessinger J, Schwartz TU, Shamoo Y, Sondermann H, Tao YJ, Tolia NH, Tsodikov OV, Westover KD, Wu H, Foster I, Fraser JS, Maia FR, Gonen T, Kirchhausen T, Diederichs K, Crosas M, Sliz P

CryptoSite: Expanding the Druggable Proteome by Characterization and Prediction of Cryptic Binding Sites.

Journal of molecular biology

Cimermancic P, Weinkam P, Rettenmaier TJ, Bichmann L, Keedy DA, Woldeyes RA, Schneidman-Duhovny D, Demerdash ON, Mitchell JC, Wells JA, Fraser JS, Sali A

High-density grids for efficient data collection from multiple crystals.

Acta crystallographica. Section D, Structural biology

Baxter EL, Aguila L, Alonso-Mori R, Barnes CO, Bonagura CA, Brehmer W, Brunger AT, Calero G, Caradoc-Davies TT, Chatterjee R, Degrado WF, Fraser JS, Ibrahim M, Kern J, Kobilka BK, Kruse AC, Larsson KM, Lemke HT, Lyubimov AY, Manglik A, McPhillips SE, Norgren E, Pang SS, Soltis SM, Song J, Thomaston J, Tsai Y, Weis WI, Woldeyes RA, Yachandra V, Yano J, Zouni A, Cohen AE

High-resolution structures of the M2 channel from influenza A virus reveal dynamic pathways for proton stabilization and transduction.

Proceedings of the National Academy of Sciences of the United States of America

Thomaston JL, Alfonso-Prieto M, Woldeyes RA, Fraser JS, Klein ML, Fiorin G, DeGrado WF

Exposing Hidden Alternative Backbone Conformations in X-ray Crystallography Using qFit.

PLoS computational biology

Keedy DA, Fraser JS, van den Bedem H

Mapping the conformational landscape of a dynamic enzyme by multitemperature and XFEL crystallography.

eLife

Keedy DA, Kenner LR, Warkentin M, Woldeyes RA, Hopkins JB, Thompson MC, Brewster AS, Van Benschoten AH, Baxter EL, Uervirojnangkoorn M, McPhillips SE, Song J, Alonso-Mori R, Holton JM, Weis WI, Brunger AT, Soltis SM, Lemke H, Gonzalez A, Sauter NK, Cohen AE, van den Bedem H, Thorne RE, Fraser JS

EMRinger: side chain-directed model and map validation for 3D cryo-electron microscopy.

Nature methods

Barad BA, Echols N, Wang RY, Cheng Y, DiMaio F, Adams PD, Fraser JS

From deep TLS validation to ensembles of atomic models built from elemental motions.

Acta crystallographica. Section D, Biological crystallography

Urzhumtsev A, Afonine PV, Van Benschoten AH, Fraser JS, Adams PD

Predicting X-ray diffuse scattering from translation-libration-screw structural ensembles.

Acta crystallographica. Section D, Biological crystallography

Van Benschoten AH, Afonine PV, Terwilliger TC, Wall ME, Jackson CJ, Sauter NK, Adams PD, Urzhumtsev A, Fraser JS

One Crystal, Two Temperatures: Cryocooling Penalties Alter Ligand Binding to Transient Protein Sites.

Chembiochem : a European journal of chemical biology

Fischer M, Shoichet BK, Fraser JS

Negative Epistasis and Evolvability in TEM-1 ß-Lactamase--The Thin Line between an Enzyme's Conformational Freedom and Disorder.

Journal of molecular biology

Dellus-Gur E, Elias M, Caselli E, Prati F, Salverda ML, de Visser JA, Fraser JS, Tawfik DS

Lineage-Specific Viral Hijacking of Non-canonical E3 Ubiquitin Ligase Cofactors in the Evolution of Vif Anti-APOBEC3 Activity.

Cell reports

Kane JR, Stanley DJ, Hultquist JF, Johnson JR, Mietrach N, Binning JM, Jónsson SR, Barelier S, Newton BW, Johnson TL, Franks-Skiba KE, Li M, Brown WL, Gunnarsson HI, Adalbjornsdóttir A, Fraser JS, Harris RS, Andrésdóttir V, Gross JD, Krogan NJ