{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:49:46Z","timestamp":1790434186076,"version":"4.1.0"},"reference-count":79,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["387697"],"award-info":[{"award-number":["387697"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Genome Canada and Genome Quebec","award":["6569"],"award-info":[{"award-number":["6569"]}]},{"name":"Canada Research Chair in Cellular Systems and Synthetic Biology"},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2022-04721"],"award-info":[{"award-number":["RGPIN-2022-04721"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000156","name":"Fonds de Recherche du Qu\u00e9bec - Sant\u00e9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>One of the front-line drug classes used to treat invasive fungal infections is echinocandins, which target the fungal-specific beta-glucan synthase (Fks). Treatment failure due to resistance often coincides with mutations in 3 protein regions defined as hotspots. Unfortunately, the scarcity of the mutational data reported, combined with the large size and membrane-embedded nature of the enzyme hinder any effort to characterize genotype-phenotype links. Recent advances in solving the structure of Fks bring us one step closer to reliable predictions of the binding modes of each echinocandin. To help with that endeavor, we used molecular dynamics simulations to develop a membrane-embedded model of Fks that captures key structural and environmental features. Our results show that the 3 hotspots shape a single solvent-exposed binding cavity, hinting at the orientation and positioning of echinocandins. This structural framework is integrated with deep-mutational scanning to comprehensively assess the impact of mutations across the 3 hotspots in the model yeast Saccharomyces cerevisiae. We elucidate several key molecular bases of resistance to the 3 most widely used echinocandins; anidulafungin, caspofungin and micafungin and provide clues to better understand intrinsic resistance of critical fungal pathogens.<\/jats:p>","DOI":"10.1093\/genetics\/iyag055","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T08:46:29Z","timestamp":1772441189000},"source":"Crossref","is-referenced-by-count":3,"title":["Mutational landscape and molecular bases of echinocandin resistance in\n                    <i>Saccharomyces cerevisiae<\/i>"],"prefix":"10.1093","volume":"233","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7681-4727","authenticated-orcid":false,"given":"Romain","family":"Durand","sequence":"first","affiliation":[{"name":"D\u00e9partement de Biochimie, de Microbiologie et de Bio-Informatique, Facult\u00e9 des Sciences et de G\u00e9nie, Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Institut de Biologie Int\u00e9grative et des Syst\u00e8mes (IBIS), Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"PROTEO, Le Regroupement Qu\u00e9b\u00e9cois de Recherche sur la Fonction, L\u2019Ing\u00e9nierie et les Applications des Prot\u00e9ines, Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Centre de Recherche sur les Donn\u00e9es Massives (CRDM), Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Institut Intelligence et Donn\u00e9es (IID), Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Centre de Recherche en Infectiologie (CRI), Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"D\u00e9partement de Biologie, Facult\u00e9 des Sciences et de G\u00e9nie, Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre G","family":"Torbey","sequence":"additional","affiliation":[{"name":"PROTEO, Le Regroupement Qu\u00e9b\u00e9cois de Recherche sur la Fonction, L\u2019Ing\u00e9nierie et les Applications des Prot\u00e9ines, Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Institut National de la Recherche Scientifique (INRS), Centre Armand-Frappier , Laval H7V 1B7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Giguere","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Biochimie, de Microbiologie et de Bio-Informatique, Facult\u00e9 des Sciences et de G\u00e9nie, Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Institut de Biologie Int\u00e9grative et des Syst\u00e8mes (IBIS), Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"PROTEO, Le Regroupement Qu\u00e9b\u00e9cois de Recherche sur la Fonction, L\u2019Ing\u00e9nierie et les Applications des Prot\u00e9ines, Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Centre de Recherche sur les Donn\u00e9es Massives (CRDM), Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Institut Intelligence et Donn\u00e9es (IID), Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Centre de Recherche en Infectiologie (CRI), Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Pageau","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Biochimie, de Microbiologie et de Bio-Informatique, Facult\u00e9 des Sciences et de G\u00e9nie, Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Institut de Biologie Int\u00e9grative et des Syst\u00e8mes (IBIS), Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"PROTEO, Le Regroupement Qu\u00e9b\u00e9cois de Recherche sur la Fonction, L\u2019Ing\u00e9nierie et les Applications des Prot\u00e9ines, Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Centre de Recherche sur les Donn\u00e9es Massives (CRDM), Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Institut Intelligence et Donn\u00e9es (IID), Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Centre de Recherche en Infectiologie (CRI), Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"D\u00e9partement de Biologie, Facult\u00e9 des Sciences et de G\u00e9nie, Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre K","family":"Dub\u00e9","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Biochimie, de Microbiologie et de Bio-Informatique, Facult\u00e9 des Sciences et de G\u00e9nie, Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Institut de Biologie Int\u00e9grative et des Syst\u00e8mes (IBIS), Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"PROTEO, Le Regroupement Qu\u00e9b\u00e9cois de Recherche sur la Fonction, L\u2019Ing\u00e9nierie et les Applications des Prot\u00e9ines, Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Centre de Recherche sur les Donn\u00e9es Massives (CRDM), Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Institut Intelligence et Donn\u00e9es (IID), Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Centre de Recherche en Infectiologie (CRI), Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"D\u00e9partement de Biologie, Facult\u00e9 des Sciences et de G\u00e9nie, Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Lag\u00fce","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Biochimie, de Microbiologie et de Bio-Informatique, Facult\u00e9 des Sciences et de G\u00e9nie, Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Institut de Biologie Int\u00e9grative et des Syst\u00e8mes (IBIS), Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"PROTEO, Le Regroupement Qu\u00e9b\u00e9cois de Recherche sur la Fonction, L\u2019Ing\u00e9nierie et les Applications des Prot\u00e9ines, Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3028-6866","authenticated-orcid":false,"given":"Christian R","family":"Landry","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Biochimie, de Microbiologie et de Bio-Informatique, Facult\u00e9 des Sciences et de G\u00e9nie, Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Institut de Biologie Int\u00e9grative et des Syst\u00e8mes (IBIS), Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"PROTEO, Le Regroupement Qu\u00e9b\u00e9cois de Recherche sur la Fonction, L\u2019Ing\u00e9nierie et les Applications des Prot\u00e9ines, Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Centre de Recherche sur les Donn\u00e9es Massives (CRDM), Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Institut Intelligence et Donn\u00e9es (IID), Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Centre de Recherche en Infectiologie (CRI), Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"D\u00e9partement de Biologie, Facult\u00e9 des Sciences et de G\u00e9nie, Universit\u00e9 Laval , Qu\u00e9bec G1V 0A6 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"key":"2026050609292486500_iyag055-B1","author":"2022. 02 Chemical Computing Group ULC","year":"2024"},{"key":"2026050609292486500_iyag055-B2","doi-asserted-by":"publisher","first-page":"2434","DOI":"10.1016\/j.jmb.2019.04.021","article-title":"Codon and Codon-pair usage tables (CoCoPUTs): facilitating genetic variation analyses and recombinant gene design","volume":"431","author":"Alexaki","year":"2019","journal-title":"J Mol Biol"},{"key":"2026050609292486500_iyag055-B3","doi-asserted-by":"publisher","first-page":"1724","DOI":"10.1093\/cid\/cit136","article-title":"Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations","volume":"56","author":"Alexander","year":"2013","journal-title":"Clin Infect Dis"},{"key":"2026050609292486500_iyag055-B4","first-page":"115","volume-title":"Methods in yeast genetics","author":"Amberg","year":"2005"},{"key":"2026050609292486500_iyag055-B5","doi-asserted-by":"publisher","first-page":"5389","DOI":"10.1021\/acs.jpcb.7b11367","article-title":"Flex ddG: Rosetta ensemble-based estimation of changes in protein-protein binding affinity upon mutation","volume":"122","author":"Barlow","year":"2018","journal-title":"J Phys Chem B"},{"key":"2026050609292486500_iyag055-B6","doi-asserted-by":"publisher","author":"B\u00e9dard","DOI":"10.1101\/2023.12.13.571438"},{"key":"2026050609292486500_iyag055-B7","doi-asserted-by":"publisher","first-page":"2338","DOI":"10.1038\/s41564-025-02084-7","article-title":"FungAMR: a comprehensive database for investigating fungal mutations associated with antimicrobial resistance","volume":"10","author":"B\u00e9dard","year":"2025","journal-title":"Nat Microbiol"},{"key":"2026050609292486500_iyag055-B8","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1093\/mmy\/myx124","article-title":"Low and constant micafungin concentrations may be sufficient to lead to resistance mutations in FKS2 gene of Candida glabrata","volume":"56","author":"Bordallo-Cardona","year":"2018","journal-title":"Med Mycol"},{"key":"2026050609292486500_iyag055-B9","doi-asserted-by":"publisher","first-page":"1972","DOI":"10.1093\/bioinformatics\/btp348","article-title":"Trimal: a tool for automated alignment trimming in large-scale phylogenetic analyses","volume":"25","author":"Capella-Guti\u00e9rrez","year":"2009","journal-title":"Bioinformatics"},{"key":"2026050609292486500_iyag055-B10","doi-asserted-by":"publisher","first-page":"e1006290","DOI":"10.1371\/journal.ppat.1006290","article-title":"Candida auris: a rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally","volume":"13","author":"Chowdhary","year":"2017","journal-title":"PLoS Pathog"},{"key":"2026050609292486500_iyag055-B11","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1128\/AAC.01542-07","article-title":"Increases in SLT2 expression and chitin content are associated with incomplete killing of Candida glabrata by caspofungin","volume":"52","author":"Cota","year":"2008","journal-title":"Antimicrob Agents Chemother"},{"key":"2026050609292486500_iyag055-B12","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1002\/jcc.10416","article-title":"A kinematic view of loop closure","volume":"25","author":"Coutsias","year":"2004","journal-title":"J Comput Chem"},{"key":"2026050609292486500_iyag055-B13","doi-asserted-by":"publisher","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle mesh ewald: an N\u22c5log(N) method for ewald sums in large systems","volume":"98","author":"Darden","year":"1993","journal-title":"J Chem Phys"},{"key":"2026050609292486500_iyag055-B14","doi-asserted-by":"publisher","first-page":"4168","DOI":"10.1093\/bioinformatics\/btz184","article-title":"Foldx 5.0: working with RNA, small molecules and a new graphical interface","volume":"35","author":"Delgado","year":"2019","journal-title":"Bioinformatics"},{"key":"2026050609292486500_iyag055-B15","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1016\/S0140-6736(03)14472-8","article-title":"Echinocandin antifungal drugs","volume":"362","author":"Denning","year":"2003","journal-title":"Lancet"},{"key":"2026050609292486500_iyag055-B16","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1038\/s41559-022-01846-4","article-title":"Asymmetrical dose responses shape the evolutionary trade-off between antifungal resistance and nutrient use","volume":"6","author":"Despr\u00e9s","year":"2022","journal-title":"Nat Ecol Evol"},{"key":"2026050609292486500_iyag055-B17","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.jsb.2009.09.009","article-title":"Influence of the g- conformation of ser and thr on the structure of transmembrane helices","volume":"169","author":"Deupi","year":"2010","journal-title":"J Struct Biol"},{"key":"2026050609292486500_iyag055-B18","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1080\/mmy.39.1.55.66","article-title":"Fungal \u03b2(1,3)-d-glucan synthesis","volume":"39","author":"Douglas","year":"2001","journal-title":"Med Mycol"},{"key":"2026050609292486500_iyag055-B19","doi-asserted-by":"publisher","first-page":"iyaf199","DOI":"10.1093\/genetics\/iyaf199","article-title":"Gy\u014dza: a Snakemake workflow for modular analysis of deep-mutational scanning data","volume":"232","author":"Durand","year":"2026","journal-title":"Genetics"},{"key":"2026050609292486500_iyag055-B20","doi-asserted-by":"publisher","first-page":"2198","DOI":"10.1021\/j100059a038","article-title":"Solvent-induced forces between two hydrophilic groups","volume":"98","author":"Durell","year":"1994","journal-title":"J Phys Chem"},{"key":"2026050609292486500_iyag055-B21","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.1093\/nar\/gkh340","article-title":"MUSCLE: multiple sequence alignment with high accuracy and high throughput","volume":"32","author":"Edgar","year":"2004","journal-title":"Nucleic Acids Res"},{"key":"2026050609292486500_iyag055-B22","doi-asserted-by":"publisher","first-page":"262","DOI":"10.3390\/jof6040262","article-title":"Rezafungin\u2014mechanisms of action, susceptibility and resistance: similarities and differences with the other echinocandins","volume":"6","author":"Garcia-Effron","year":"2020","journal-title":"J Fungi (Basel)"},{"key":"2026050609292486500_iyag055-B23","doi-asserted-by":"publisher","first-page":"2305","DOI":"10.1128\/AAC.00262-08","article-title":"A naturally occurring proline-to-alanine amino acid change in Fks1p in Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis accounts for reduced echinocandin susceptibility","volume":"52","author":"Garcia-Effron","year":"2008","journal-title":"Antimicrob Agents Chemother"},{"key":"2026050609292486500_iyag055-B24","doi-asserted-by":"publisher","first-page":"3690","DOI":"10.1128\/AAC.00443-09","article-title":"Effect of Candida glabrata FKS1 and FKS2 mutations on echinocandin sensitivity and kinetics of 1,3-\u03b2-D-glucan synthase: implication for the existing susceptibility breakpoint","volume":"53","author":"Garcia-Effron","year":"2009","journal-title":"Antimicrob Agents Chemother"},{"key":"2026050609292486500_iyag055-B25","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1128\/AAC.01162-08","article-title":"Correlating echinocandin MIC and kinetic inhibition of fks1 mutant glucan synthases for Candida albicans: implications for interpretive breakpoints","volume":"53","author":"Garcia-Effron","year":"2009","journal-title":"Antimicrob Agents Chemother"},{"key":"2026050609292486500_iyag055-B26","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/s41586-020-2649-2","article-title":"Array programming with NumPy","volume":"585","author":"Harris","year":"2020","journal-title":"Nature"},{"key":"2026050609292486500_iyag055-B27","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1038\/s41586-023-05856-5","article-title":"Structural and mechanistic insights into fungal \u03b2-1,3-glucan synthase FKS1","volume":"616","author":"Hu","year":"2023","journal-title":"Nature"},{"key":"2026050609292486500_iyag055-B28","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/nmeth.4067","article-title":"CHARMM36m: an improved force field for folded and intrinsically disordered proteins","volume":"14","author":"Huang","year":"2017","journal-title":"Nat Methods"},{"key":"2026050609292486500_iyag055-B29","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1109\/MCSE.2007.55","article-title":"Matplotlib: a 2D graphics environment","volume":"9","author":"Hunter","year":"2007","journal-title":"Comput Sci Eng"},{"key":"2026050609292486500_iyag055-B30","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1002\/jcc.20945","article-title":"CHARMM-GUI: a web-based graphical user interface for CHARMM","volume":"29","author":"Jo","year":"2008","journal-title":"J Comput Chem"},{"key":"2026050609292486500_iyag055-B31","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1128\/EC.00082-12","article-title":"Topological and mutational analysis of Saccharomyces cerevisiae Fks1","volume":"11","author":"Johnson","year":"2012","journal-title":"Eukaryot Cell"},{"key":"2026050609292486500_iyag055-B32","doi-asserted-by":"publisher","first-page":"3774","DOI":"10.1128\/AAC.01811-10","article-title":"New fks hot spot for acquired echinocandin resistance in Saccharomyces cerevisiae and its contribution to intrinsic resistance of Scedosporium species","volume":"55","author":"Johnson","year":"2011","journal-title":"Antimicrob Agents Chemother"},{"key":"2026050609292486500_iyag055-B33","doi-asserted-by":"publisher","first-page":"e202314728","DOI":"10.1002\/anie.202314728","article-title":"Reshaping echinocandin antifungal drugs to circumvent glucan synthase point-mutation-mediated resistance","volume":"63","author":"Jospe-Kaufman","year":"2024","journal-title":"Angewandte Chemie (International ed. in English)"},{"key":"2026050609292486500_iyag055-B34","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"2026050609292486500_iyag055-B35","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1002\/pro.3280","article-title":"Improvements to the APBS biomolecular solvation software suite","volume":"27","author":"Jurrus","year":"2018","journal-title":"Protein Sci"},{"key":"2026050609292486500_iyag055-B36","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.1128\/AAC.00020-09","article-title":"Role for Fks1 in the intrinsic echinocandin resistance of Fusarium solani as evidenced by hybrid expression in Saccharomyces cerevisiae","volume":"53","author":"Katiyar","year":"2009","journal-title":"Antimicrob Agents Chemother"},{"key":"2026050609292486500_iyag055-B37","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1016\/j.tips.2024.02.007","article-title":"Targeting Fks1 proteins for novel antifungal drug discovery","volume":"45","author":"Kumar","year":"2024","journal-title":"Trends Pharmacol Sci"},{"key":"2026050609292486500_iyag055-B38","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1093\/molbev\/msy096","article-title":"MEGA X: molecular evolutionary genetics analysis across computing platforms","volume":"35","author":"Kumar","year":"2018","journal-title":"Mol Biol Evol"},{"key":"2026050609292486500_iyag055-B39","doi-asserted-by":"publisher","first-page":"3626","DOI":"10.1128\/AAC.00123-14","article-title":"Positions and numbers of FKS mutations in Candida albicans selectively influence in vitro and in vivo susceptibilities to echinocandin treatment","volume":"58","author":"Lackner","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"key":"2026050609292486500_iyag055-B40","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1093\/molbev\/msn067","article-title":"An improved general amino acid replacement matrix","volume":"25","author":"Le","year":"2008","journal-title":"Mol Biol Evol"},{"key":"2026050609292486500_iyag055-B41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s44259-023-00007-2","article-title":"Molecular mechanisms governing antifungal drug resistance","volume":"1","author":"Lee","year":"2023","journal-title":"NPJ Antimicrob Resist."},{"key":"2026050609292486500_iyag055-B42","doi-asserted-by":"publisher","first-page":"2054","DOI":"10.1038\/s41467-025-57152-7","article-title":"Cryo-EM structure of the \u03b2-1,3-glucan synthase FKS1-rho1 complex","volume":"16","author":"Li","year":"2025","journal-title":"Nat Commun"},{"key":"2026050609292486500_iyag055-B43","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1093\/bioinformatics\/9.6.745","article-title":"Protein sequence alignments: a strategy for the hierarchical analysis of residue conservation","volume":"9","author":"Livingstone","year":"1993","journal-title":"Comput Appl Biosci"},{"key":"2026050609292486500_iyag055-B44","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1002\/pro.4219","article-title":"Spatial arrangement of proteins in planar and curved membranes by PPM 3.0","volume":"31","author":"Lomize","year":"2022","journal-title":"Protein Sci"},{"key":"2026050609292486500_iyag055-B45","doi-asserted-by":"publisher","first-page":"325","DOI":"10.2144\/000113672","article-title":"Extraction of genomic DNA from yeasts for PCR-based applications","volume":"50","author":"L\u00f5oke","year":"2011","journal-title":"Biotechniques"},{"key":"2026050609292486500_iyag055-B46","doi-asserted-by":"publisher","first-page":"2851","DOI":"10.1128\/AAC.49.7.2851-2856.2005","article-title":"Cryptococcus neoformans resistance to echinocandins: (1,3)beta-glucan synthase activity is sensitive to echinocandins","volume":"49","author":"Maligie","year":"2005","journal-title":"Antimicrob Agents Chemother"},{"key":"2026050609292486500_iyag055-B47","doi-asserted-by":"publisher","first-page":"5671","DOI":"10.1128\/MCB.15.10.5671","article-title":"Differential expression and function of two homologous subunits of yeast 1,3-beta-D-glucan synthase","volume":"15","author":"Mazur","year":"1995","journal-title":"Mol Cell Biol"},{"key":"2026050609292486500_iyag055-B48","doi-asserted-by":"crossref","first-page":"56","DOI":"10.25080\/Majora-92bf1922-00a","volume-title":"Proceedings of the 9th Python in science conference","author":"McKinney","year":"2010"},{"key":"2026050609292486500_iyag055-B49","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1002\/jcc.540130805","article-title":"Settle: an analytical version of the SHAKE and RATTLE algorithm for rigid water models","volume":"13","author":"Miyamoto","year":"1992","journal-title":"J Comput Chem"},{"key":"2026050609292486500_iyag055-B50","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.cell.2004.06.013","article-title":"Exploration of essential gene functions via titratable promoter alleles","volume":"118","author":"Mnaimneh","year":"2004","journal-title":"Cell"},{"key":"2026050609292486500_iyag055-B51","doi-asserted-by":"publisher","first-page":"33","DOI":"10.12688\/f1000research.29032.2","article-title":"Sustainable data analysis with Snakemake","volume":"10","author":"M\u00f6lder","year":"2021","journal-title":"F1000Res"},{"key":"2026050609292486500_iyag055-B52","doi-asserted-by":"publisher","first-page":"1206056","DOI":"10.3389\/fpubh.2023.1206056","article-title":"Direct detection of drug-resistant Mycobacterium tuberculosis using targeted next generation sequencing","volume":"11","author":"Murphy","year":"2023","journal-title":"Front Public Health"},{"key":"2026050609292486500_iyag055-B53","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1093\/cid\/civ933","article-title":"Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America","volume":"62","author":"Pappas","year":"2016","journal-title":"Clin Infect Dis"},{"key":"2026050609292486500_iyag055-B54","first-page":"2825","article-title":"Scikit-learn: machine learning in Python","volume":"12","author":"Pedregosa","year":"2011","journal-title":"J Mach Learn Res"},{"key":"2026050609292486500_iyag055-B55","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1002\/pro.3943","article-title":"UCSF ChimeraX: structure visualization for researchers, educators, and developers","volume":"30","author":"Pettersen","year":"2021","journal-title":"Protein Sci"},{"key":"2026050609292486500_iyag055-B56","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1093\/ofid\/ofy358","article-title":"Twenty years of the SENTRY antifungal surveillance program: results for Candida species from 1997-2016","volume":"6","author":"Pfaller","year":"2019","journal-title":"Open Forum Infect Dis"},{"key":"2026050609292486500_iyag055-B57","doi-asserted-by":"publisher","first-page":"4690","DOI":"10.1128\/AAC.03255-14","article-title":"Role of FKS mutations in Candida glabrata: MIC values, echinocandin resistance, and multidrug resistance","volume":"58","author":"Pham","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"key":"2026050609292486500_iyag055-B58","doi-asserted-by":"publisher","first-page":"044130","DOI":"10.1063\/5.0014475","article-title":"Scalable molecular dynamics on CPU and GPU architectures with NAMD","volume":"153","author":"Phillips","year":"2020","journal-title":"J Chem Phys"},{"key":"2026050609292486500_iyag055-B59","doi-asserted-by":"publisher","first-page":"2265","DOI":"10.3390\/molecules25092265","article-title":"Predicting drug resistance using deep mutational scanning","volume":"25","author":"Pines","year":"2020","journal-title":"Molecules"},{"key":"2026050609292486500_iyag055-B60","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1021\/acs.jcim.1c01514","article-title":"Comparative molecular dynamics simulation studies of realistic eukaryotic, prokaryotic, and archaeal membranes","volume":"62","author":"Pogozheva","year":"2022","journal-title":"J Chem Inf Model"},{"key":"2026050609292486500_iyag055-B61","doi-asserted-by":"publisher","first-page":"e32","DOI":"10.1093\/nar\/gkq953","article-title":"Metaphors: orthology and paralogy predictions from multiple phylogenetic evidence using a consistency-based confidence score","volume":"39","author":"Pryszcz","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"2026050609292486500_iyag055-B62","doi-asserted-by":"publisher","first-page":"e0014223","DOI":"10.1128\/cmr.00142-23","article-title":"Advancements and challenges in antifungal therapeutic development","volume":"37","author":"Puumala","year":"2024","journal-title":"Clin Microbiol Rev"},{"key":"2026050609292486500_iyag055-B63","doi-asserted-by":"publisher","first-page":"pdb.prot086827","DOI":"10.1101\/pdb.prot086827","article-title":"CRISPR-Cas9 Genome engineering in Saccharomyces cerevisiae cells","volume":"2016","author":"Ryan","year":"2016","journal-title":"Cold Spring Harb Protoc"},{"key":"2026050609292486500_iyag055-B64","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/0021-9991(77)90098-5","article-title":"Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes","volume":"23","author":"Ryckaert","year":"1977","journal-title":"J Comput Phys"},{"key":"2026050609292486500_iyag055-B65","author":"Schr\u00f6dinger","year":"2015"},{"key":"2026050609292486500_iyag055-B66","doi-asserted-by":"publisher","first-page":"5421","DOI":"10.1128\/AAC.00096-14","article-title":"Target enzyme mutations confer differential echinocandin susceptibilities in Candida kefyr","volume":"58","author":"Staab","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"key":"2026050609292486500_iyag055-B67","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1080\/14756366.2022.2050224","article-title":"Echinocandins\u2014structure, mechanism of action and use in antifungal therapy","volume":"37","author":"Szyma\u0144ski","year":"2022","journal-title":"J Enzyme Inhib Med Chem"},{"key":"2026050609292486500_iyag055-B68","doi-asserted-by":"publisher","first-page":"433","DOI":"10.7164\/antibiotics.43.433","article-title":"Cilofungin inhibition of (1-3)-beta-glucan synthase: the lipophilic side chain is essential for inhibition of enzyme activity","volume":"43","author":"Taft","year":"1990","journal-title":"J Antibiot (Tokyo)"},{"key":"2026050609292486500_iyag055-B69","doi-asserted-by":"publisher","first-page":"2272","DOI":"10.1093\/bioinformatics\/btz921","article-title":"Logomaker: beautiful sequence logos in python","volume":"36","author":"Tareen","year":"2020","journal-title":"Bioinformatics"},{"key":"2026050609292486500_iyag055-B70","doi-asserted-by":"publisher","first-page":"D368","DOI":"10.1093\/nar\/gkad1011","article-title":"AlphaFold protein structure database in 2024: providing structure coverage for over 214 million protein sequences","volume":"52","author":"Varadi","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"2026050609292486500_iyag055-B71","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1038\/s41592-019-0686-2","article-title":"Scipy 1.0: fundamental algorithms for scientific computing in python","volume":"17","author":"Virtanen","year":"2020","journal-title":"Nat Methods"},{"key":"2026050609292486500_iyag055-B72","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.fgb.2009.09.003","article-title":"Fungal echinocandin resistance","volume":"47","author":"Walker","year":"2010","journal-title":"Fungal Genet Biol"},{"key":"2026050609292486500_iyag055-B73","doi-asserted-by":"publisher","first-page":"3021","DOI":"10.21105\/joss.03021","article-title":"Seaborn: statistical data visualization","volume":"6","author":"Waskom","year":"2021","journal-title":"J Open Source Softw"},{"key":"2026050609292486500_iyag055-B74","author":"World Health Organization","year":"2022"},{"key":"2026050609292486500_iyag055-B75","doi-asserted-by":"publisher","first-page":"1997","DOI":"10.1002\/jcc.23702","article-title":"CHARMM-GUI Membrane Builder toward realistic biological membrane simulations","volume":"35","author":"Wu","year":"2014","journal-title":"J Comput Chem"},{"key":"2026050609292486500_iyag055-B76","doi-asserted-by":"publisher","first-page":"863","DOI":"10.15252\/msb.20156660","article-title":"Pooled-matrix protein interaction screens using barcode fusion genetics","volume":"12","author":"Yachie","year":"2016","journal-title":"Mol Syst Biol"},{"key":"2026050609292486500_iyag055-B77","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/s44259-025-00102-6","article-title":"Hotspot gene conversion between FKS1 and FKS2 in echinocandin resistant Candida glabrata serial isolates","volume":"3","author":"Zajac","year":"2025","journal-title":"NPJ Antimicrob Resist."},{"key":"2026050609292486500_iyag055-B78","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1038\/s41592-022-01585-1","article-title":"US-align: universal structure alignments of proteins, nucleic acids, and macromolecular complexes","volume":"19","author":"Zhang","year":"2022","journal-title":"Nat Methods"},{"key":"2026050609292486500_iyag055-B79","doi-asserted-by":"publisher","first-page":"eadh7820","DOI":"10.1126\/sciadv.adh7820","article-title":"Structure of a fungal 1,3-\u03b2-glucan synthase","volume":"9","author":"Zhao","year":"2023","journal-title":"Sci Adv"}],"container-title":["GENETICS"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/genetics\/advance-article-pdf\/doi\/10.1093\/genetics\/iyag055\/67196071\/iyag055.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/genetics\/article-pdf\/233\/1\/iyag055\/67196071\/iyag055.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/genetics\/article-pdf\/233\/1\/iyag055\/67196071\/iyag055.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T13:29:33Z","timestamp":1778074173000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/genetics\/article\/doi\/10.1093\/genetics\/iyag055\/8503201"}},"subtitle":[],"editor":[{"given":"B","family":"Andrews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,3,2]]},"references-count":79,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,3,2]]},"published-print":{"date-parts":[[2026,5,6]]}},"URL":"https:\/\/doi.org\/10.1093\/genetics\/iyag055","relation":{},"ISSN":["1943-2631"],"issn-type":[{"value":"1943-2631","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,5]]},"published":{"date-parts":[[2026,3,2]]},"article-number":"iyag055"}}