Steered Molecular Dynamics Simulation Of Alpha-catenin

Protein plays an important role in the overall biological world, from a variety of chemical reactions catalyzed to various tissues in vivo.There are many different conformational states in regulating the biological process of life activities, mutual conversion between these different conformational states regulate normal life activities. Adherens junction is the main form to connect cells, which is consisted of many different proteins and adjusts the growth and integrity of the biological tissues.alpha-catenin is an important component of the adherens junction. In vivo, alpha-catenin plays a part in mechanical transducer, when it is subjected to external force, alpha-catenin can convert this mechanical signals into chemical signals.Combination between alpha-catenin and vinculin regulate the connection of cells. In order to study the structural changes in the external force, alpha-catenin has been stretched at constant velocity with the magnetic tweezers. The results show that alpha-catenin is unfolded in three characteristic steps, which is stretched at a constant velocity. Further studies showe that the binding of vinculin and alpha-catenin occurs in the first step, and their binding prevents alpha-catenin refolding. However, the detailes of structure changing are not clear in this process. To understand the deeper problem of alpha-catenin unfolding process, we use NAMD(nonascale molecular dynamics) to simulate the alpha-catenin with constant velocity stretching, and observe the changes in the atomic level.With the enhancement of computing power, the molecular dynamics simulation method is widely used to study some properties of the protein. On the one hand, we can observe mutual transformation in different structures using molecular dynamics simulation. On the other hand, it can show up the changes of kinetics and thermodynamics for proteins. The experimental results can be well carried out and supplemented by molecular dynamics simulation. The method can predict the tendency for the transformation of the protein and provide a good theoretical basis.In this thesis, we use NAMD to simulate the alpha-catenin. In the simulation process, we fixed alpha carbon atom at one end and stretched another alpha carbon atom to observe the structural change with external force. We draw the following conclusions:First, when alpha-catenin is stretched at a constant velocity(amino acid sequence 275-735), the first unfolding process occurs at about 450±30p N. In this process, alpha-catenin is pulled into two parts, and expose its vinculin binding sites(amino acid sequence:344) due to the structural change. Meanwhile, the main force is hydrophobic interaction.Second, the amino acid sequence 275-635 of alpha-catenin is stretched at a constant velocity. By force spectrum analysis, we obtain there are two different unfolding phenomenons,and of which the forces are about 430±20p N. With worm-like-chain model, comparing the two phases at the back of solutions folding stage of alpha-catenin with amino acid sequence 275-735 by magnetic tweezers stretching, we find its corresponding force of about 16 p N with experiment.Third, the simulation of amino acid sequence 275-878 alpha-catenin was analyzed, and we obtain that there is a force about 650±50p N, which is greater than the force needed in exposing its vinculin binding site of the amino acid sequence leucine 344.So we can infer that when we stretch the whole alpha-catenin at a constant velocity, making vinculin binding sites expose we need a greater force than 5p N in stretching amino acid sequence 275-735 of alpha-catenin.