Sun gano ɗimbin 'masu sarrafa nesa' na sunadaran da za a iya amfani da su don nemo magunguna masu inganci

christina garridoSAURARA

Wata sabuwar dabarar da wata kungiya ta kimiya ta kirkira a Cibiyar Ka'idojin Halittar Halittu (CRG) a Barcelona ta gano akwai tarin 'masu sarrafa nesa' wadanda ke sarrafa aikin sunadaran kuma ana iya amfani da su azaman makasudi don samun ingantattun magunguna. kuma yana da inganci a cikin cututtuka daban-daban kamar ciwon hauka, ciwon daji da cututtuka masu yaduwa.

Waɗannan 'masu sarrafa nesa' a kimiyance aka sani da wuraren allosteric. Waɗannan su ne na'urori masu nisa waɗanda ke da nisa daga wurin aikin furotin, amma suna da ikon daidaitawa ko daidaita shi", Júlia Domingo, marubucin farko na binciken, wanda aka buga wannan Laraba a cikin mujallar "Nature", ya bayyana wa ABC. Kuma ya ƙara da wani misalin: "Kamar dai da wannan remote ɗin zaka iya kunna ko kashe fitilar ko kuma daidaita ƙarfin hasken."

A wannan yanayin inda ya yi niyyar toshewa ko daidaita ayyukan sunadaran da ke kula da canjin aikinsu a cikin tsare. Misali, game da ciwon daji, sunadaran da suka sami maye gurbi sun canza aikinsu, suna yin hakan ba tare da wata matsala ba kuma tantanin halitta yana girma ta hanyar da ba a saba gani ba. A yawancin lokuta, babu magungunan da za su iya daidaitawa ko toshe wannan mummunan aiki ko, idan akwai, ba su da takamaiman kuma ana fitar da su daga wasu sunadaran da ke aiki akai-akai.

A al'adance, masu farautar miyagun ƙwayoyi sun ƙirƙira jiyya waɗanda ke kaiwa wurin aiki na furotin, wanda ƙananan yankinsa ke haifar da halayen sinadarai inda aka ɗaure. Alamar wadannan kwayoyi, wadanda aka fi sani da Orthosteric drugs, shi ne, wuraren aiki na sunadaran da yawa sun yi kama da juna kuma magungunan sun daure tare da hana yawancin sunadaran a lokaci guda, har ma wadanda suke aiki akai-akai kuma ba su da sha'awar tabawa, wanda ya haifar da rashin jin daɗi. na iya haifar da illa.

"A can ya shiga cikin tunanin allosteria da yuwuwar da zai iya tsara magunguna. Abu mai ban sha'awa game da shafukan allosteric shine cewa sun kasance na musamman ga kowane furotin. Idan waɗannan shafukan yanar gizo na allosteric sun sami wani ɓangare na farfajiyar sunadaran inda magani zai iya sauka, zai zama musamman musamman ga furotin. Za mu iya yin burin samun ingantattun magunguna,” in ji mai binciken.

“Ba wai kawai mun gano cewa waɗannan wuraren ba da magani suna da yawa, amma akwai tabbacin cewa ana iya sarrafa su ta hanyoyi daban-daban. Maimakon kunna su da kashe su kawai, za mu iya canza ayyukansu kamar ma'aunin zafi da sanyio. Ta fuskar aikin injiniya, kamar mun bugi zinari ne, domin yana ba mu ɗaki mai yawa don tsara 'magungunan wayo' waɗanda ke yin mummunan aiki kuma su tsallake masu kyau, "in ji André Faure, mai bincike na postdoctoral a CRG. da farko co - marubucin labarin.

Hoto mai girma uku yana nuna furotin ɗan adam PSD95-PDZ3 daga mabanbantan ra'ayi. Ana nuna kwayar halitta tana ɗaure zuwa wurin aiki cikin rawaya. Launi mai launin shuɗi zuwa ja yana nuna yiwuwar wuraren allostericHoto mai girma uku yana nuna furotin ɗan adam PSD95-PDZ3 daga mabanbantan ra'ayi. Ana nuna kwayar halitta tana ɗaure zuwa wurin aiki cikin rawaya. Launi mai launin shuɗi zuwa ja yana nuna yiwuwar rukunin yanar gizo - André Faure/ChimeraX

Don wannan binciken, ƙungiyar ta yi amfani da hanyar da za ta ba su damar ɗaukar furotin da tsarin tsari da kuma gamuwa na duniya tare da duk shafuka. Don yin wannan, sun zaɓi sunadaran sunadaran guda biyu masu yawa a cikin furotin mu na ɗan adam. "50% na furotin saman yana da damar allosteric. Hanyarmu ta ba da damar yin atlas na rukunin yanar gizo, wanda zai sa aiwatar da aikin neman magunguna masu inganci sosai,” in ji Júlia Domingo.

Marubutan binciken sun kirkiro wata dabara da ake kira PCA mai zurfi biyu (ddPCA), wacce suka bayyana a matsayin "gwajin karfi mai karfi." "Muna karya abubuwa da gangan a dubban hanyoyi daban-daban don samar da cikakken hoto na yadda wani abu ke aiki," in ji Farfesa Farfesa Ben Lehner, Coordinator of the Systems Biology Program a CRG kuma marubucin binciken. “Kamar idan ka yi zargin tarkacen tartsatsin ba ta da kyau, amma maimakon kawai ka bincika, makanikin zai kwashe motar gaba daya ya duba dukkan sassan daya bayan daya. Ta hanyar nazarin abubuwa dubu goma lokaci guda, za mu gano dukkan abubuwan da ke da mahimmanci.

Bayan haka, muna amfani da algorithms na hankali don fassara sakamakon lab.

Ɗaya daga cikin manyan fa'idodin hanyar, ban da sauƙaƙe tsarin da ake buƙata don nemo wuraren allosteric, shine cewa fasaha ce mai araha kuma mai isa ga kowane ɗakin binciken bincike a duniya. "Yana buƙatar kawai samun damar yin amfani da abubuwan da ake amfani da su na kwayoyin halitta, samun damar yin amfani da jerin DNA da kwamfuta. Tare da waɗannan abubuwa guda uku, kowane dakin gwaje-gwaje a cikin watanni 2-3, tare da ƙaramin kasafin kuɗi, na iya aiwatar da wannan gwaji akan furotin na sha'awar da suke so, ”in ji Júlia Domingo. Fatan masu binciken shine masana kimiyyar mu za su yi amfani da wannan dabarar wajen yin taswirori cikin sauri da kuma taswirorin abubuwan da ke tattare da sunadarai na ɗan adam ɗaya bayan ɗaya. "Idan muna da isassun bayanai watakila wata rana za mu iya tafiya mataki daya gaba kuma mu yi hasashen daga jerin furotin zuwa aiki. Yi amfani da waɗannan bayanan don jagorantar su azaman hanyoyin kwantar da hankali don tsinkaya idan wani canji a cikin furotin zai ragu zuwa cuta, ”in ji mai binciken.