Protein structure analysis

Proteins : is made of chain of amino acids ( amino acid= monomers) therefor the protein is polymers .
The proteins are made up of carbon, hydrogen, oxygen, and nitrogen.
Amino acid :

1. Protein structure analysis Prepared by: Anfal Izaldeen ALKATEEB

2. Protein structure Proteins : is made of chain of amino acids ( amino acid= monomers) therefor the protein is polymers . The proteins are made up of carbon, hydrogen, oxygen and nitrogen. Amino acid : Amino acid — amino acid Peptide bond with removal of water

3. Protein analysis protein shape determines function. Amino acid order determines the shape( conformation) of protein. Conformation determines function. Function depends on its ability to recognize and bind a molecule. Many of amino acids jointed by peptide bond formed polypeptide chain which is not brunched. (amino acid in poly peptide is called residue .)

4. The protein divided into groups Globular protein: these are molecules there are often spherical in shape have a chemical function ex: enzyme . Fibrous protein: these have structural role. They give strength or elasticity to a particular tissue ex: collagen and keratin in hair.

5. Protein structure Proteins are long sequences formed out of 20 different amino acid residues that in physiological conditions adopt a unique 3-D structure. Knowledge of the protein structure allows the investigation of biological processes more directly ,with higher resolution and finer detail. Bio chemists have distinguished several levels of structure organization of proteins .

6. Proteins levels Primary structure : a sequence of amino acid in a polypeptides chain. Secondary structure : refers to highly regular local sub strictures. These sec. str. Are defined by patterns of hydrogen bonds between the main- chain peptide groups. Both of α helix and β sheets represent away of saturating all the hydrogen bond donors and accepted in the peptide backbone. Bonds a helix is the most common secondary Structure .

7. Tertiary protein structure Tertiary structure is the 3D conformation of polypeptides. The α helixes and β- pleated- sheets are folded into a compact globular structure. This structure elements when arrangement in space , creating structural Motifs and folds ( tertiary structure ). The knowledge of the 3D structure of polypeptides gives researchers very important information to infer the function of the protein in the cell structural functions ;catalysis in chemical reactions; transport and storage; regulatory functions; gene transcription control and recognition functions

8. 3D protein structure analysis The shape is maintain by hydrogen bonds and the strong bonds disulfide bridge which form between the sulphur containing amino acid molecule. The difficulty in determining and finding out the 3-D structure of proteins has generated a large discrepancy between the volume of data (sequences of amino acid residues) generated by the Genome Projects and the number of 3-D structures of proteins which are currently known. Only a tiny portion of protein sequences have experimentally solved three-dimensional structures. The function of protein is depend on its tertiary structure if this distributed, its losses its activity.

9. 3D protein structure the folding which formed by α helix and β sheets is driven by the nonspecific hydrophobic interactions( the burial of hydrophobic residues from water), but the structure is stable only when the parts of protein domains are locked into a place by specific tertiary interaction such as salt bridges ,hydrogen bonds and tight packing of side chains and disulfide bond. the disulfide bonds are extremely rare in cytosolic protein, since the cytosolic is generally a reducing environment.

10. Domain An independent unit of the 3D protein structure is called domain. Polypeptide chain containing more than 200 residues usually fold into two or more globular clusters( this cluster is domain). Fundamental functional and 3D structure of proteins Domains often have a specific function such as the binding of small molecules. Many domains are structurally independent units that have the characteristic of small globular protein. A protein domains is assigned a certain type of fold Domains with the same fold may or may not be related to each other functionally .

11. 3D protein structure analysis Determination of tertiary structure The known protein structure have come to light through: X rays crystallographic studies. Nuclear magnetic resonance studies. The atomic coordinates of most of these structures are deposited in a database known as the Protein Data Bank (PDB). It allows the tertiary structures of variety of proteins to be analyzed and compared . The PDB have been classified into more than 1000 different unique folds.

12. Quaternary structure The protein consists more than one polypeptides. The different of polypeptide chains bind to gather to form a whole molecule. The biological function of some molecules is determined by multiple polypeptide. . arrangement of polypeptide sub unite is quaternary by non covalent Ex: insulin is made up of two chains while hemoglobin is made up of four chains.

13. 3 D structure analysis Interaction Stabilizing 3 D Structure The final shape is determined by a variety of bonding interactions between the side chains on the amino acids. The interactions occur between R group & R group and backbone. Hydrogen bonds , Ionic bonds , Disulphide bridges hydrophobic interaction ( often in interior of protein) . Covalent bonds : disulfide bridge formed between the sulfhydryl group (SH) of cystein amino acid.

14. 3 D modeling of protein Protein modeling : provide a solid bases for: Structure based drug design rational design of proteins with increased stability or novel function They can be used to examine sequence-structure-function relationships, interactions, active sites , and more. Three dimensional structures provide a wealth of information on the biological function and the evolutionary history of macromolecules. Successful model building requires at least one experimentally solved 3D structure (template) that has a significant amino acid sequence similarity to the target sequence. Various structural genomics initiatives were started in the last few years, aiming to speed up the elucidation of new protein structures.

15. Proteins modeling Homology protein Portion of 2 proteins with similar amino acids : *conserved region. * highly similar proteins may have same basic function Homology modeling Comparative modeling of protein To predict protein structure based on known 3D shape protein as a templet .

16. Homology modeling The structure of protein is determined by its amino acid sequence and Structure is much more conserved than sequence during evolution. Homology modeling based on two major observation

17. What is the homology modeling Predicts the 3D structure of a given protein sequence (target) based on an alignment to one or more known protein structure(templates). if similarity between the target sequence and the template sequence is detected, structural similarity can be assumed. in general 30% sequence identity is required to generate an useful model

18. 2. A b initio modeling A b initio modeling conducts a conformational search under the guidance of a designed energy function. This procedure usually generates a number of possible conformation (structure decoys). and final models are selected from them.

19. a successful AB initio modeling depends on 3 factors: 1. a accurate energy function with which the native structure of protein corresponds to the most thermodynamically stable state, compared to all possible decoy structures. 2. an efficient search method which can quickly identify the two- energy states through conformation search. 3. selection of native- like model from a pool of decoy structure.

20. 3. Threading modeling of protein Protein threading , also known as fold recognition is a method of protein modeling which is used to model those proteins which have the same fold as a proteins of known structure but do not have homologous proteins with known structure. Protein threading is an effective method for identifying the compatibility of a new protein sequence with a 3D fold that might not be obvious from normal sequence comparisons. It differs from the homology modeling method of structure predication as it ( protein threading) is used for proteins which don’t have their homologous protein structure deposited in the Protein Data Bank(PDB). Whereas homology modeling is used for those proteins which do.

21. Threading works by using statistical knowledge of the relationship between the structures deposited in the PDB and the sequence of the protein which one wishes to model . The prediction is made by "threading" (i.e. placing, aligning) each amino acid in the target sequence to a position in the template structure, and evaluating how well the target fits the template. After the best-fit template is selected, the structural model of the sequence is built based on the alignment with the chosen template. Protein threading is based on two basic observations: that the number of different folds in nature is fairly small (approximately 1300); and that 90% of the new structures submitted to the PDB in the past three years have similar structural folds to ones already in the PDB.

22. Threading

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