단백질 지혜 : 용 워크 벤치

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Smadbeck, J., Peterson, M. B., Khoury, G. A., Taylor, M. S., Floudas, C. A. Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules. J. Vis. Exp. (77), e50476, doi:10.3791/50476 (2013).

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Abstract

드 노보 단백질 설계의 목적은 기본 순서를 기준으로 같은 결합력, 작용제 또는 길항제의 행동이나 안정성 등의 특정 속성, 개선에 필요한 3 차원 구조로 접을 것 아미노산 서열을 찾을 수 있습니다. 단백질 디자인은 현재 발전 약물 설계 및 발견의 중심에 자리 잡고 있습니다. 뿐만 아니라 단백질 디자인은 잠재적으로 유용한 약물 표적에 대한 예측을 제공하지만, 그것은 또한 단백질 폴딩 과정과 단백질 - 단백질 상호 작용에 대한 우리의 이해를 향상 않습니다. 같은 방향 진화 등의 실험 방법은 단백질 디자인에서 성공을 보여 주었다. 그러나, 이러한 방법은 tractably 검색 할 수 있습니다 제한된 순서 공백으로 제한됩니다. 반면, 전산 설계 전략 특성과 다양한 기능을 포함 시퀀스의 훨씬 더 큰 집합의 심사 할 수 있습니다. 우리는 전산 드 노보 단백질 디자인 METHO의 범위를 개발했습니다단백질 설계의 몇 가지 중요한 영역을 다루는 능력 DS. 이러한 증가 바인딩 선호도 증가 안정성과 단지에 대한 단량체 단백질의 디자인이 (가) 있습니다.

넓은 위해 이러한 방법을 전파하는 것은 우리가 단백질 지혜 (현재 사용 http://www.proteinwisdom.org ), 단백질 설계 문제의 다양한 자동화 된 방법을 제공하는 도구입니다. 구조 템플릿은 디자인 프로세스를 초기화하기 위해 제출됩니다. 설계의 첫 번째 단계는 시퀀스 공간에 잠재적 인 에너지의 최소화를 통해 안정성을 향상을 목표로 최적화 순서 선택 단계입니다. 선택한 시퀀스는 다음 배 특이 무대와 결합 친화 단계를 통해 실행됩니다. 프로세스의 각 단계에 대한 염기 서열의 순위 정렬 된 목록은 함께 관련 설계 구조로, 디자인의 포괄적 인 양적 평가와 함께 사용자를 제공합니다. 여기에서 우리는 세부 사항 O를 제공합니다F 각 설계 방법뿐만 아니라, 방법의 사용을 통해 달성 몇 가지 주목할만한 실험 성공.

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