Researches On Outer Membrane Protein Functional Structure

?-strand type transmembrane protein are called outer membrane protein(abbreviated OMP),because this type of protein is only found in biological cells,mitochondria,and gram-bacteria on the outer membrane of the chloroplast.Outer membrane protein in quantity and diversity were significantly lower than ?-helical transmembrane proteins,but this protein also plays an irreplaceable role in the life body,serve as outer membrane channel,Ion,even small molecular biological functions such as transfer,resistance to antibiotics,vaccine design,and are of great significance in the study of diagnosis and treatment of cancer.Therefore,the outer membrane protein research is a vital part to further insight into the micro-life activities,and explore the mechanism of life.Biological studies have shown that protein structure determine their biological function,protein function discovery is usually dependent on the accurate structure of protein,outer membrane protein also follows this rule.However,the transmembrane segment of outer membrane protein locates in the phospholipid layer,which significantly effects their spatial structure.This special biochemical property decided the structure of outer membrane protein could not be obtained as soluble protein by crystal experiments.It is the reason that known structure amount of outer membrane protein is far less than solvent protein,even significantly less than full alpha type transmembrane protein,which becomes the obstacle to understand the function of outer membrane protein.The rapid development of high-throughput sequencing technologies resulting in abounding outer membrane protein sequences,therefore,protein structure prediction is a certainly practical approach to offer more structures.The most importance of this research is predicting the functional structures for outer membrane protein based on definite data,including the topology structure,spatial structure,inner residual interaction structure and outer material structure,by which overall protein function could be further predicted.In this paper,we reference water dissolved protein structure forecast methods,focusing on abstracting the structural specific features for outer membrane proteins, from which to design and achieve functional structure researches,and strengthening special spatial structure and special biochemical property of outer membrane protein in algorithm,finally reducing the negative effect resulting from small number of structure samples,improving the functional structure prediction precision.The corresponding research work follows the steps as:1)Based on structural characteristics and outer membrane protein samples and comparison of outer membrane protein and biochemical properties with water-soluble protein,extraction of various features of outer membrane proteins of specific and quantified through contrast filter can significantly improve the characteristics of the outer membrane protein structure prediction accuracy.2)based on the condition that outer membrane protein has small sample structure dataset,we compare three main approaches for protein structure prediction: de novo methods,homology modeling and fold recognition methods,applicability of the outer membrane protein structure prediction problem,the final choice of fold recognition methods for reference,and formed according to the structure of the outer membrane protein structure prediction using their specific characteristics.Finally,we generate the methodology of predicting functional structure of outer membrane protein by using structure-specific features.3)Introduce Deep Learning method to outer membrane protein topology structure prediction for the first time,and design and implement corresponding method OMPTDN.The work aims to present the topology structure of outer membrane protein which is vital important structure-specific feature distinguished with soluble protein.It will not only offer the available feature for the next researches,but also the foundation to research the structure and function of outer membrane protein4)Introduce a segment-based alignment method to outer membrane protein,we continuously strengthen the structural specific features of outer membrane protein,integrate topological structure,sequence conservation features,phospholipid layer accessibility features such as local and global features and sequence,optimum processes and global correction results.Outer membrane protein fold recognition methods first designed and implemented TMFRB(Transmembrane Fold Recogition Beta).Experimentals proved that,this method can efficiently identify sequence similarity and outer membrane proteins of unknown structure of the protein,outer membrane protein conformational model to further provide strong support.5)In order to overcome the lack of outer membrane proteins of known structure template,outer membrane protein structure modeling based on the template provided at TMFRB,also needs more structural information in order to improve prediction accuracy,within the outer membrane protein conformation of amino acid interaction provides credible information.Before using the outer membrane proteins of specific features designed and realized OMPcontact amino acids within the outer membrane protein interaction prediction methods(Outer Membrane Protein Contact),fill a gap in the corresponding tool.Experimental results show that OMPcontact can effectively predict the interactions within the outer membrane protein amino acids,prediction accuracy is significantly superior water-soluble protein prediction tool.6)Predict the molecular-protein interaction site in non-transmembrane part of outer membrane protein,including various drug-protein interaction site.These sites could choose particular type of molecular passing through to cross the channel on outer membrane.We design and implement the corresponding prediction method OMPsite to fill in the blank in this field.Above studies formed a complete research framework for outer membrane functional structure,contribute to outer membrane protein structure feature extraction and selection,topology structure prediction,fold recognition method,strengthen the conformational information,and interaction site prediction,as well provide effective methods and tools.This study not only has laid a good foundation to outer membrane protein functional structure researches,but also provides a new perspective for all types of transmembrane protein research,its research procedures and methods can be directly applied to ?-helical transmembrane proteins,it is promising to further promote transmembrane protein researches on structure and function.