CENTRAL-ATOM-VECTOR-BASED PROTEIN-LIGAND BINDING STRUCTURE ANALYSIS METHOD OF ARTIFICIAL INTELLIGENCE NEW DRUG PLATFORM

• Main Authors: JUNG, Jong Sun, JUNG, Hee Hoon, HONG, Jong Hui, YOON, Seung Min
• Format: Patent
• Language: English; French; Korean
• Published: 28.03.2024
• Subjects: INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTEDFOR SPECIFIC APPLICATION FIELDS; PHYSICS

The present invention relates to discovery of an active ingredient for new drug development. The present invention comprises the steps of: (A) constructing a database of the three-dimensional conformers of an analyte (compound); (B) extracting the coordinates of the core ring of a ligand from the 3D binding structure of a target protein-ligand; (C) extracting the coordinates of a core ring from each of the docking poses forming the conformers of a compound to be screened for; (D) aligning the core ring of the docking poses of the compound and the core ring of the ligand, thereby obtaining docking coordinate information about the compound; (E) calculating a protein-ligand interaction (PLI) score depending on the docking coordinate information about the compound, thereby selecting a docking pose; and (F) repeatedly performing steps (A) to (E) on the conformers of a preset compound. In the present invention, flexible docking is simplified such that the processing time of protein-ligand 3D structure analysis, which previously took several minutes to several hours per substance structure, is reduced to be from several seconds to tens of seconds, and thus, compared to a conventional analysis technique, 10 to 100 times more substances can be analyzed in the same amount of time. La présente invention concerne la découverte d'un principe actif pour le développement d'un nouveau médicament. La présente invention comprend les étapes consistant : (A) construire une base de données des conformères tridimensionnels d'un analyte (composé); (B) extraire les coordonnées de l'anneau central d'un ligand de la structure de liaison 3D d'un ligand-protéine cible; (C) extraire les coordonnées d'un anneau central de chacune des poses d'accueil formant les conformères d'un composé à cribler; (D) aligner l'anneau central des poses d'accueil du composé et l'anneau central du ligand, ce qui permet d'obtenir des informations de coordonnées d'accueil concernant le composé; (E) calculer un score d'interaction protéine-ligand (PLI) en fonction des informations de coordonnées d'accueil concernant le composé, ce qui permet de sélectionner une pose d'accueil; et (F) effectuer de manière répétée les étapes (A) à (E) sur les conformères d'un composé prédéfini. Dans la présente invention, l'accueil flexible est simplifié de telle sorte que le temps de traitement de l'analyse de structure 3D ligand-protéine, qui prenait auparavant plusieurs minutes à plusieurs heures par structure de substance, est réduit pour être de quelques secondes à des dizaines de secondes et, ainsi, par comparaison avec une technique d'analyse classique, 10 à 100 fois plus de substances peuvent être analysées dans la même quantité de temps. 본 발명은 신약개발을 위한 유효물질을 발굴에 관한 것으로, 본 발명은 (A) 분석대상 물질(화합물)의 3차원 컨포머(conformer)를 데이터베이스화하여 구축하는 단계와; (B) 표적단백질-리간드의 3D 결합 구조로부터 리간드(ligand)의 코어링(core ring)의 좌표를 추출하는 단계와; (C) 스크리닝 대상 화합물의 컴포머(conformer)를 구성하는 각각의 결합위치(pose)들로부터 코어링(core ring) 좌표를 추출하는 단계와; (D) 상기 화합물(compound)의 결합위치(pose)에 대한 코어링(core ring)과 리간드(ligand)의 코어링(core ring)을 정렬(align)하여, 화합물(compound)의 결합(docking) 좌표정보를 획득하는 단계와; (E) 화합물(compound)의 결합(docking) 좌표정보에 따라 단백질-리간드 간 상호연관 지수(PLI score)를 산출하여, 결합위치(docking pose)를 선정하는 단계; 그리고 (F) 상기 (A) 내지 (E) 단계를 기 설정된 화합물(compound)의 컨포머(conformer)들에 대하여 반복 수행하는 단계;를 포함하여 수행된다. 이와 같은 본 발명에 의하면, 본 발명에서는 물질구조당 수분~수시간 소요되던 protein-ligand 3D 구조 분석을 flexible docking 작업을 간소화 하여, 처리 소요시간을 수 초 내지 수십 초 수준으로 저감화 하여, 종래의 분석 기술에 대비하여, 10 내지 100배 이상의 물질을 동일한 시간에 분석하는 것이 가능해지는 효과가 있다.