Date of Award
Fall 8-5-2023
Degree Type
Thesis
Department
Chemistry and Biochemistry
Abstract
Protein to protein interactions are significant to various biological processes, functioning, and the regulation of cells and organisms. Proteins perform essential cellular tasks and often work together in complexes, enabling specific functions like enzymatic activity, signal transduction, DNA replication, and cell division. These interactions are important in signaling pathways, allowing proteins to interact sequentially, leading to specific cellular responses. Some proteins rely on chaperones to fold correctly, and protein to protein interactions enhance stability, preventing degradation.
Researchers at Stanford University School of Medicine discovered that EvC syndrome is related to a malfunction in the Hedgehog (Hh) signaling pathway. They found that Hh agonists stimulate the interaction between the ciliary protein EVC2 and Smoothened (Smo) at a specific ciliary compartment called the EVC zone. This complex is essential for proper Hh signal transmission and plays an important role in the molecular basis of EvC syndrome and Weyers Acrofacial Dysostosis. EVC and EVC2 are found together in a complex, and it is assumed that they interact with each other to influence their activities.
To identify protein to protein interactions, a combination of computational tools and software were used. Alphafold, a learning-based system, predicts the 3D structure of proteins, providing valuable insights into their conformation and potential interaction sites. ClusPro and ZDock, protein docking software, were used to predict the binding mode between two proteins and generate potential complexes. Prodigy, a web server that calculates the binding affinity between two proteins, was used to assess the strength of the predicted interactions. Furthermore, Pymol, a molecular visualization tool, aided in visualizing and analyzing the 3D structures of proteins and their interactions, facilitating the exploration of potential binding sites and intermolecular interactions.
In the fragment region (451-750), we observed probable interactions between mEVC and mEVC2 involving 11 amino acids: LEU-540, LYS-541, PRO- 544, GLU-545, SER-548, LEU-549, PRO-550, VAL-551, ALA-552, GLU-553, and THR-556. These contacts included van der Waals forces (hydrophobic) and electrostatic interactions, with some of them forming hydrogen bonds. In most of the complexes, EVC2 did not make direct contact with the P-loop and Leucine zipper region of EVC.
The study provided valuable insights into the amino acids responsible for the interaction between mEVC and mEVC2 proteins, highlighting the importance of specific residues and the effects of mutations on their interaction dynamics. However, obtaining consistent interaction interfaces across various models was challenging, possibly due to limitations in generating repeated or sufficient models using computational tools and software.
Repository Citation
MAMUN, MD ATIKUL ISLAM, "Bioinformatic Analysis of the Interaction Of EVC And EVC2 Proteins" (2023). Electronic Theses and Dissertations. 555.
https://scholarworks.sfasu.edu/etds/555
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
