Rebuilding Of Missing Atom Information In The Cryo-EM Structure By MODELLER

As a functional complex,which main components are protein and Ribonucleic Acid(RNA),spliceosome plays an important role in the process of gene expression in transformation from Pre-mRNA to mRNA.At present,the observation of structure of the protein has achieved to a resolution of 3.6 angstroms by means of the method of Cryo-EM.Due to the limitation of experimental methods,protein crystallization conditions and other aspects,the tertiary structure of the protein still can not be measured perfectly,which reflected in the measured structure still contains a large number of residues missing.Because of its tertiary structure affects the function and character of the protein directly,thus obtaining a complete tertiary structure is particularly important.Theoretically,we can use the homology modeling method that based on experimentally got primary structure to rebuild the tertiary structure of the protein and reconstruct the structure of the spliceosome,so as to complete the incomplete part of the spliceosome.In my work,homologous modeling method was used to reconstruct 16 peptides with residues missing of the human spliceosome.And we combined the quality score of the peptides reconstructed and the results of the analysis to their structures to filter out the results with excellent scores and more reasonable structures.Thereafter,the atomic coordinate information of the spliceosome is completed and improved.These will provide the reliable tertiary structure of the human spliceosome for the subsequent studies of the spliceosome such as molecular docking and dynamics simulation.During this process,scripting is used to simplify the complicated pretreatment and post-analysis process in homology modeling.In this paper,homology modeling and scripting are combined to automate the process of pretreatment and data analysis,which greatly facilitates and simplifies the related work of missing fragments reconstruction of other biomolecules such as proteins and nucleic acids.Especially for the great larger system of proteins with lots of missing fragment,it greatly facilitates the homology modeling.In a longer-term perspective,this job has the important meaningful for the treatment of related diseases and the discovery of new drug.