Principal Component Analysis Of BamA All-Atom And Coarse-Grained Trajectories

Bam( β-barrel assembly machine) complex is responsible for the assembling of β-barrel membrane proteins that locate in the outer membranes of Gram-negative bacteria and of the mitochondria and chloroplasts of eukaryotes. β-barrel membrane proteins are related to Gram-negative bacteria pathogenicity. So diseases caused by Gram-negative bacteria can be treated through studies of the assembling mechanism of Bam complex. Bam complex consists of five components, which are Bam A, Bam B, Bam C,Bam D,Bam E. Bam A is the central component of the complex and comprises of a β-barrel domain and five polypeptide transport-associated domains. It belongs to membrane proteins. Bam A is our study object. First, we use molecular dynamics simulation method to obtain trajectories of Bam A. Then we use principal component analysis method to gain principal motion modes of Bam A. Finally we compare the motion modes with the information in the papers and find connections between them. Above all, we want to propose what a role does Bam A play in the Bam complex assembling machinery. Molecular dynamics simulation is a method depended on Newton’s law through computer technology for simulate atoms’ dynamic processes. We can acquire atoms’ movement details that can’t be easy to get by experiments. Molecular dynamics simulation can provide new sights for solving theory and experiment problems. Due to the limit of computers’ operating power and memory, we can’t get access to atoms’ movement details and large time scale simultaneously in the process of molecular dynamics simulation. So we build both all-atom system and coarse-grained system for Bam A. Coarse-grained model is a simplification of all-atom model. It maps several atoms into one bead. Although it may miss some information of atoms level details, it reduces freedom of the system and raises compute speed. Therefore we can get microsecond time scale and even above. This is hard for all-atom simulation. Principal component analysis is a dimensionality reduction method. It extracts main factors in the correlative messages and remains origin information as much as possible. We do principal component analysis for both all-atom system and coarse-grained trajectories. We obtain similar motion mode: the first four POTRA domains rotate around the junction of the fourth and fifth POTRA domains. This also confirm the accuracy of our coarse-grained model. We have known some information from papers: Bam complex can be divided into two sub complexes, Bam AB and Bam CDE; POTRA2-4 has interactions with Bam B; P5 has interactions with Bam D. This is consistent with our motion mode. Bam complex assembling machinery can be outlined to recognition, folding and insertion to the substrates. The motion mode we get maybe relate to the folding or insertion process. The motion mode may complete the process with other lipoproteins in the complex. According to several mechanisms mentioned in the papers, our motion mode may help substrates get to the lumen of Bam A β-barrel or to position that is going to insert the outer membrane. Above all, our work is of some importance for learning about the roles that Bam A play in the Bam complex assembling.