{"id":"https://openalex.org/W4408903742","doi":"https://doi.org/10.1021/acs.jcim.5c00011","title":"Energetics of Expanded PAM Readability by Engineered Cas9-NG","display_name":"Energetics of Expanded PAM Readability by Engineered Cas9-NG","publication_year":2025,"publication_date":"2025-03-27","ids":{"openalex":"https://openalex.org/W4408903742","doi":"https://doi.org/10.1021/acs.jcim.5c00011","pmid":"https://pubmed.ncbi.nlm.nih.gov/40146191"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.5c00011","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c00011","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5025224920","display_name":"Shreya Bhattacharya","orcid":"https://orcid.org/0000-0001-5291-331X"},"institutions":[{"id":"https://openalex.org/I1317621060","display_name":"Indian Institute of Technology Guwahati","ror":"https://ror.org/0022nd079","country_code":"IN","type":"education","lineage":["https://openalex.org/I1317621060"]}],"countries":["IN"],"is_corresponding":false,"raw_author_name":"Shreya Bhattacharya","raw_affiliation_strings":["Department of Biosciences and Bioengineering","Indian Institute of Technology Guwahati"],"affiliations":[{"raw_affiliation_string":"Department of Biosciences and Bioengineering","institution_ids":[]},{"raw_affiliation_string":"Indian Institute of Technology Guwahati","institution_ids":["https://openalex.org/I1317621060"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5032959524","display_name":"Priyadarshi Satpati","orcid":"https://orcid.org/0000-0002-0391-3580"},"institutions":[{"id":"https://openalex.org/I1317621060","display_name":"Indian Institute of Technology Guwahati","ror":"https://ror.org/0022nd079","country_code":"IN","type":"education","lineage":["https://openalex.org/I1317621060"]}],"countries":["IN"],"is_corresponding":true,"raw_author_name":"Priyadarshi Satpati","raw_affiliation_strings":["Department of Biosciences and Bioengineering","Indian Institute of Technology Guwahati"],"affiliations":[{"raw_affiliation_string":"Department of Biosciences and Bioengineering","institution_ids":[]},{"raw_affiliation_string":"Indian Institute of Technology Guwahati","institution_ids":["https://openalex.org/I1317621060"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5032959524"],"corresponding_institution_ids":["https://openalex.org/I1317621060"],"apc_list":null,"apc_paid":null,"fwci":3.1277,"has_fulltext":false,"cited_by_count":4,"citation_normalized_percentile":{"value":0.9101849,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":97,"max":98},"biblio":{"volume":"65","issue":"7","first_page":"3628","last_page":"3639"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10502","display_name":"Advanced Memory and Neural Computing","score":0.9882000088691711,"subfield":{"id":"https://openalex.org/subfields/2208","display_name":"Electrical and Electronic Engineering"},"field":{"id":"https://openalex.org/fields/22","display_name":"Engineering"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T10502","display_name":"Advanced Memory and Neural Computing","score":0.9882000088691711,"subfield":{"id":"https://openalex.org/subfields/2208","display_name":"Electrical and Electronic Engineering"},"field":{"id":"https://openalex.org/fields/22","display_name":"Engineering"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10878","display_name":"CRISPR and Genetic Engineering","score":0.9812999963760376,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10472","display_name":"Semiconductor materials and devices","score":0.9739999771118164,"subfield":{"id":"https://openalex.org/subfields/2208","display_name":"Electrical and Electronic Engineering"},"field":{"id":"https://openalex.org/fields/22","display_name":"Engineering"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/energetics","display_name":"Energetics","score":0.8426252603530884},{"id":"https://openalex.org/keywords/readability","display_name":"Readability","score":0.7396013736724854},{"id":"https://openalex.org/keywords/crispr","display_name":"CRISPR","score":0.4503006041049957},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.4242878258228302},{"id":"https://openalex.org/keywords/computational-biology","display_name":"Computational biology","score":0.35828661918640137},{"id":"https://openalex.org/keywords/computer-science","display_name":"Computer science","score":0.35612231492996216},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.2700667977333069},{"id":"https://openalex.org/keywords/biochemistry","display_name":"Biochemistry","score":0.1881798803806305},{"id":"https://openalex.org/keywords/programming-language","display_name":"Programming language","score":0.1753520965576172},{"id":"https://openalex.org/keywords/ecology","display_name":"Ecology","score":0.10868436098098755},{"id":"https://openalex.org/keywords/gene","display_name":"Gene","score":0.08488601446151733}],"concepts":[{"id":"https://openalex.org/C97514900","wikidata":"https://www.wikidata.org/wiki/Q719597","display_name":"Energetics","level":2,"score":0.8426252603530884},{"id":"https://openalex.org/C2778143727","wikidata":"https://www.wikidata.org/wiki/Q1820650","display_name":"Readability","level":2,"score":0.7396013736724854},{"id":"https://openalex.org/C98108389","wikidata":"https://www.wikidata.org/wiki/Q412563","display_name":"CRISPR","level":3,"score":0.4503006041049957},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.4242878258228302},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.35828661918640137},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.35612231492996216},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.2700667977333069},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.1881798803806305},{"id":"https://openalex.org/C199360897","wikidata":"https://www.wikidata.org/wiki/Q9143","display_name":"Programming language","level":1,"score":0.1753520965576172},{"id":"https://openalex.org/C18903297","wikidata":"https://www.wikidata.org/wiki/Q7150","display_name":"Ecology","level":1,"score":0.10868436098098755},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.08488601446151733}],"mesh":[{"descriptor_ui":"D000076987","descriptor_name":"CRISPR-Associated Protein 9","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D000076987","descriptor_name":"CRISPR-Associated Protein 9","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D000076987","descriptor_name":"CRISPR-Associated Protein 9","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D000076987","descriptor_name":"CRISPR-Associated Protein 9","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D000076987","descriptor_name":"CRISPR-Associated Protein 9","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D000076987","descriptor_name":"CRISPR-Associated Protein 9","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D004247","descriptor_name":"DNA","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D004247","descriptor_name":"DNA","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D004247","descriptor_name":"DNA","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D004247","descriptor_name":"DNA","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D004247","descriptor_name":"DNA","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D004247","descriptor_name":"DNA","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D008958","descriptor_name":"Models, Molecular","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008958","descriptor_name":"Models, Molecular","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009154","descriptor_name":"Mutation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009154","descriptor_name":"Mutation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013297","descriptor_name":"Streptococcus pyogenes","qualifier_ui":"Q000201","qualifier_name":"enzymology","is_major_topic":false},{"descriptor_ui":"D013297","descriptor_name":"Streptococcus pyogenes","qualifier_ui":"Q000201","qualifier_name":"enzymology","is_major_topic":false},{"descriptor_ui":"D013816","descriptor_name":"Thermodynamics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013816","descriptor_name":"Thermodynamics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015202","descriptor_name":"Protein Engineering","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D015202","descriptor_name":"Protein Engineering","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D053837","descriptor_name":"DNA Cleavage","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D053837","descriptor_name":"DNA Cleavage","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D064130","descriptor_name":"CRISPR-Associated Proteins","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D064130","descriptor_name":"CRISPR-Associated Proteins","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D064130","descriptor_name":"CRISPR-Associated Proteins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D064130","descriptor_name":"CRISPR-Associated Proteins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D064130","descriptor_name":"CRISPR-Associated Proteins","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D064130","descriptor_name":"CRISPR-Associated Proteins","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1021/acs.jcim.5c00011","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c00011","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},{"id":"pmid:40146191","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/40146191","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of chemical information and modeling","raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Affordable and clean energy","score":0.5600000023841858,"id":"https://metadata.un.org/sdg/7"}],"awards":[{"id":"https://openalex.org/G4940731251","display_name":null,"funder_award_id":"YSS/2015/000024","funder_id":"https://openalex.org/F4320334771","funder_display_name":"Science and Engineering Research Board"},{"id":"https://openalex.org/G862458981","display_name":null,"funder_award_id":"1901286","funder_id":"https://openalex.org/F4320322724","funder_display_name":"Ministry of Education, India"}],"funders":[{"id":"https://openalex.org/F4320322724","display_name":"Ministry of Education, India","ror":"https://ror.org/048xjjh50"},{"id":"https://openalex.org/F4320334771","display_name":"Science and Engineering Research Board","ror":"https://ror.org/03ffdsr55"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":69,"referenced_works":["https://openalex.org/W1625910593","https://openalex.org/W1966867657","https://openalex.org/W1970196890","https://openalex.org/W1971548202","https://openalex.org/W1972758026","https://openalex.org/W1975769356","https://openalex.org/W1976499671","https://openalex.org/W1978393297","https://openalex.org/W1988101725","https://openalex.org/W1989195611","https://openalex.org/W2001062582","https://openalex.org/W2011131418","https://openalex.org/W2012231377","https://openalex.org/W2014661586","https://openalex.org/W2021520922","https://openalex.org/W2027408247","https://openalex.org/W2029667189","https://openalex.org/W2038758364","https://openalex.org/W2045435533","https://openalex.org/W2056432311","https://openalex.org/W2067174909","https://openalex.org/W2084005259","https://openalex.org/W2096261947","https://openalex.org/W2107959600","https://openalex.org/W2109154308","https://openalex.org/W2124812694","https://openalex.org/W2130479394","https://openalex.org/W2142515819","https://openalex.org/W2150981663","https://openalex.org/W2169244146","https://openalex.org/W2194181707","https://openalex.org/W2237671266","https://openalex.org/W2321640944","https://openalex.org/W2331161041","https://openalex.org/W2510638623","https://openalex.org/W2550897879","https://openalex.org/W2554763217","https://openalex.org/W2656673982","https://openalex.org/W2741956225","https://openalex.org/W2774078190","https://openalex.org/W2785694952","https://openalex.org/W2793309516","https://openalex.org/W2803581084","https://openalex.org/W2885445984","https://openalex.org/W2889513238","https://openalex.org/W2912830833","https://openalex.org/W2915198336","https://openalex.org/W2921808963","https://openalex.org/W2923287387","https://openalex.org/W2947777875","https://openalex.org/W2952694437","https://openalex.org/W3007852986","https://openalex.org/W3011718018","https://openalex.org/W3013504322","https://openalex.org/W3073482037","https://openalex.org/W3099414985","https://openalex.org/W3104651685","https://openalex.org/W4235410425","https://openalex.org/W4239632189","https://openalex.org/W4245053291","https://openalex.org/W4281652498","https://openalex.org/W4302362355","https://openalex.org/W4313367009","https://openalex.org/W4313894924","https://openalex.org/W4315754647","https://openalex.org/W4318979003","https://openalex.org/W4387267294","https://openalex.org/W4394725624","https://openalex.org/W4407302902"],"related_works":["https://openalex.org/W4387497383","https://openalex.org/W2948807893","https://openalex.org/W2899084033","https://openalex.org/W2778153218","https://openalex.org/W2748952813","https://openalex.org/W1531601525","https://openalex.org/W4391375266","https://openalex.org/W1964661231","https://openalex.org/W4213036952","https://openalex.org/W4377030018"],"abstract_inverted_index":{"The":[0,81,103,165,294],"energetic":[1],"basis":[2],"for":[3,86,310],"the":[4,39,43,52,68,87,114,119,124,135,138,142,179,187,193,196,217,229,236,252,269,276,282,302,308,311],"enhanced":[5],"PAM":[6,55,163,180,198,255,259],"(protospacer":[7],"adjacent":[8],"motif)":[9],"readability":[10],"in":[11,54,71,91,186,242],"engineered":[12],"Cas9-NG":[13,98],"(a":[14],"variant":[15],"of":[16,42,67,118,141,195,238,251,271,284,304,316],"Cas9":[17],"from":[18,178],"<i>Streptococcus":[19],"pyogenes</i>":[20],"(<i>Sp</i>Cas9))":[21],"with":[22,65,134,228],"seven":[23,69],"mutations:":[24],"(R1335V,":[25],"E1219F,":[26],"D1135V,":[27,152],"L1111R,":[28,153],"T1337R,":[29],"G1218R,":[30],"and":[31,97,108,116,154,161,169,191,205,221,278,280,291,313],"A1322R)":[32],"remains":[33],"a":[34,48,288],"fundamental":[35],"unsolved":[36],"problem.":[37],"Utilizing":[38],"X-ray":[40],"structure":[41],"precatalytic":[44],"complex":[45],"(<i>Sp</i>Cas9:sgRNA:dsDNA)":[46],"as":[47,174],"template,":[49],"we":[50],"calculated":[51],"changes":[53],"(TGG,":[56],"TGA,":[57],"TGT,":[58],"or":[59],"TGC)":[60],"binding":[61,129,181,209],"affinity":[62],"(\u0394\u0394<i>G</i>)":[63,84],"associated":[64],"each":[66],"mutations":[70,150,219,239],"<i>Sp</i>Cas9":[72,96,107,317],"through":[73,265],"rigorous":[74],"alchemical":[75],"simulations":[76],"(sampling":[77],"\u223c":[78],"53":[79],"\u03bcs).":[80],"underlying":[82],"thermodynamics":[83],"accounts":[85],"experimentally":[88],"observed":[89],"differences":[90],"DNA":[92,101,109,128,208],"cleavage":[93],"activity":[94],"between":[95,106,275],"across":[99],"various":[100],"substrates.":[102],"interaction":[104,245],"energies":[105],"are":[110,171],"significantly":[111],"influenced":[112],"by":[113,130,147,200,210],"type":[115],"location":[117,237],"amino":[120],"acid":[121],"mutations.":[122],"Notably,":[123],"R1335V":[125,143],"mutation":[126,144],"disfavors":[127],"disrupting":[131],"critical":[132],"interactions":[133,160,185,227,274,286],"PAM.":[136],"However,":[137],"destabilizing":[139],"effect":[140],"is":[145,240,262],"mitigated":[146],"four":[148],"advantageous":[149],"(E1219F,":[151],"T1337R),":[155],"which":[156],"primarily":[157,263],"introduce":[158],"nonbase-specific":[159,273],"enhance":[162],"readability.":[164],"hydrophobic":[166,292],"substitutions":[167],"(E1219F":[168],"D1135V)":[170],"particularly":[172],"impactful,":[173],"they":[175],"exclude":[176],"solvent":[177],"pocket,":[182],"strengthening":[183],"electrostatic":[184,213,285],"low":[188],"dielectric":[189],"medium":[190],"increasing":[192],"stability":[194],"noncognate":[197,254,305],"complexes":[199,256],"\u223c2-5":[201],"kcal/mol.":[202],"Additionally,":[203],"L1111R":[204],"T1337R":[206],"facilitate":[207],"forming":[211],"direct":[212],"contacts.":[214],"In":[215],"contrast,":[216],"charge":[218],"G1218R":[220],"A1322R":[222],"do":[223],"not":[224],"effectively":[225],"promote":[226],"negatively":[230],"charged":[231],"DNA,":[232],"clearly":[233],"demonstrating":[234],"that":[235,249,297],"crucial":[241],"shaping":[243],"these":[244],"energetics.":[246],"We":[247],"demonstrated":[248],"stabilization":[250],"Cas9-NG:":[253],"enables":[257],"broader":[258],"recognition.":[260],"This":[261],"achieved":[264],"two":[266],"mechanisms:":[267],"(1)":[268],"establishment":[270],"new":[272],"protein":[277],"nucleotides":[279],"(2)":[281],"enhancement":[283],"within":[287],"relatively":[289],"dry":[290],"pocket.":[293],"findings":[295],"revealed":[296],"mutation-induced":[298],"desolvation":[299],"can":[300],"improve":[301],"recognition":[303],"PAMs,":[306],"paving":[307],"way":[309],"rational":[312],"innovative":[314],"design":[315],"mutants.":[318]},"counts_by_year":[{"year":2025,"cited_by_count":4}],"updated_date":"2025-12-28T23:10:05.387466","created_date":"2025-10-10T00:00:00"}