Investigating the environmental differences between parallel and anti-parallel beta sheets
|has title::Investigating the environmental differences between parallel and anti-parallel beta sheets|
|Student name:||student name::Punto Bawono|
Investigating the environmental differences between parallel and anti parallel beta sheets
Beta sheet is the second most common form of regular secondary structure in proteins. They are often bringing together parts of the protein that are separated along the backbones. This structure is made up from a combination of several regions of the polypeptide chain called beta strands which are laterally connected to each other by means of hydrogen bonds. Beta strands can interact in two ways to form a beta sheet. Either the amino acids in the adjacent beta strands can all run in the same biochemical direction (parallel), or in alternating directions (antiparallel). Parallel and antiparallel arrangements of strands in a sheet differ in hydrogen bond pattern between strands, type of chain connectivity and amino acid preferences. Even though there have several studies done on beta sheets, the roles of parallel and anti parallel beta sheets are not yet well understood.
Natural beta sheet proteins are usually soluble, but fragments of beta sheets usually form aggregates. The edges of beta sheets are dangerous because they are already in the right conformation to interact with any other beta strands they encounter. Proteins usually have features that prevent their beta sheets from forming interactions with other beta strands. Due to this characteristic, beta sheets are sometimes associated with the formation of various protein aggregates, such as amyloids. Amyloids are fibrous protein aggregates that may play an important role in neurodegenerative diseases, such as Alzheimer’s disease.
The research process will be divided in two steps. Firstly I am going to survey structural features of beta sheets such as hydrogen bonding pattern and solvent accessibility in all protein structures in the PDB; secondly I am going to do statistical analysis on the survey result to see whether there are significant differences between parallel and anti parallel beta sheets.
To analyze the hydrogen bonding pattern and solvent accessibility of beta sheets in a protein, a program called DSSP will be used. The DSSP (Define Secondary Structure of Proteins) was designed by Wolfgang Kabsch and Chris Sander, the original paper of DSSP was published in 1983. This program does not predict protein structure but instead it defines secondary structure, geometrical features, hydrogen bonding pattern and solvent accessibility of proteins based on their atomic coordinates. DSSP requires a file in PDB format as the input. PDB file format provides description and annotation of the three dimensional structures properties of proteins, such as atomic coordinates, crystallographic structure factors and NMR experimental data.
Since in this research we have to analyze all proteins in the PDB, we need a small program to automate the process of reading all entries in the PDB, putting all the PDB files into DSSP and analyzing the output files of DSSP. This program will be written in C programming language.
The aim of this research is to determine whether there are significant differences in the structure of parallel and antiparallel beta sheets, and whether these differences have any effect on the stability of the sheets. If there are indeed significant differences in the structure of parallel and anti parallel beta sheets, then I would like to construct a hypothesis regarding the possible relations between the structural differences and the functions of parallel and anti parallel beta sheets.
My internship research will take place The Centre for Integrative Bioinformatics VU (IBIVU). The duration of this research is 4 months starting 1 April 2010, in which I will fork for 40 hours per week. During this research I will be supervised by Dr. Sanne Abeln.
April Reading literatures and designing the program
May Writing and testing the program
June Analyzing the results
July Writing project report