Putting the Pieces Together Integrative Modeling Platform Software for Structure Determination of Macromolecular Assemblies 英文参考文献.docVIP

CommunityPage PuttingthePiecesTogether:IntegrativeModeling PlatformSoftwareforStructureDeterminationof MacromolecularAssemblies DanielRussel1,KerenLasker1,2,BenWebb1,JavierVela′zquez-Muriel1,ElinaTjioe1,DinaSchneidman- Duhovny1,BretPeterson3,AndrejSali1* 1DepartmentofBioengineeringandTherapeuticSciences,DepartmentofPharmaceuticalChemistry,CaliforniaInstituteforQuantitativeBiosciences(QB3),Universityof California, San Francisco, San Francisco, California, United States of America, 2Raymond and Beverly Sackler Faculty of Exact Sciences, Blavatnik School of Computer Science,TelAvivUniversity,Tel-Aviv,Israel,3Google,MountainView,California,UnitedStatesofAmerica Introduction nuclear magnetic resonance (NMR) data and X-ray crystallographic structures of constituent proteins [2]. The structure of chromatin around the alpha-globin gene was assembled from so-called 5C data (chromosome conformation capture car- bon copy) [3]. The value of integrative modelingisillustratedbyitsapplicationto the yeast nuclear pore complex (NPC) [4,5].Thesheersizeandflexibilityofthe NPCmakesitallbutimpossibletosolveits molecular architecture by conventional atomic resolution techniques, such as X- ray crystallography. However, integrating informationfrommultiplesources,includ- ingstoichiometryfromproteinquantifica- tion,proteinproximitiesfromsubcomplex purification, protein positions from im- muno-EM, sedimentation analysis that sheds light on protein and subcomplex shapes, and the overall NPC shape from EM, resulted in an ensemble of medium- exit from the nucleus of macromolecules, and also shed light on its evolution [4,6–8]. Building models of a biological system that are consistent with the myriad data available is one of the key challenges in biology. Modeling the structure and dy- namicsofmacromolecularassemblies,for example, can give insights into how biological systems work, evolved, might becontrolled,andevendesigned.Model- ing can also suggest future experiments. Unfortunately,