Secondary structural elements & ramachandran plot. Gly and Pro Specially treated

1. S.Prasanth Kumar, Bioinformatician Proteins Secondary Structural Elements with special attention to Ramachandran Plot S.Prasanth Kumar Dept. of Bioinformatics Applied Botany Centre (ABC) Gujarat University, Ahmedabad, INDIA www.facebook.com/Prasanth Sivakumar FOLLOW ME ON ACCESS MY RESOURCES IN SLIDESHARE prasanthperceptron CONTACT ME [email_address]

2. Coined : Linderstrom-Lang and Schnellman 1959 Primary & Secondary Structure Primary structure refers to the linear sequence of amino acid residues in a polypeptide chain MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH Secondary structure refers to the arrangements of the primary amino acid sequence into motifs such as alpha helices, beta sheets, and coils (or loops)

3. Secondary Structure : Example

4. Tertiary Structure The tertiary structure is the three-dimensional arrangement formed by packing secondary structure elements into globular domains

5. Quaternary Structure Quaternary structure involves the arrangement of several polypeptide chains

6. Peptide Bond & Phi-Psi Angles Phi is the angle around the N-Ca bond Psi is the angle around the Ca-C’ bond In glycine , the R group is a hydrogen and thus amino acid is not chiral

7. Secondary Structure Glycine is an exceptional amino acid because it has the flexibility to occur at phi-psi combinations that are not tolerated for other amino acids For most amino acids the phi and psi angles are constrained to allowable regions in which there is a high propensity for particular secondary structures to form Linus Pauling and Robert Corey (1951) described the secondary structures : alpha helix and beta pleated sheets from hemoglobin, keratins, etc Type of Helices Alpha 3.10* Pi Amino acid per turn 3.6 3.0 4.4 Occurrence in structure 97% 3 % rare *more tightly packed

8. Ramachandran Plot A Ramachandran plot displays the phi and psi angles for essentially all amino acids in a protein ( proline and glycine are not displayed ) Why Glycine and Proline are not treated ? Glycine’s has more flexibility, phi-psi combinations not tolerated Proline is extremely unlikely to occur in an a helix, and it is often positioned at a turn You Should Add later information Secondary-Structure Prediction Programs

9. Ramachandran Plot

11. Glycine and Proline Glycine has a much wider low-energy area because it does not have a Ca atom Proline has its side chain covalently bound to backbone amine; hence its phi angle is limited to the range of phi = -60° +/- 20° Glycine is formally nonpolar, its very small side chain makes no real contribution to hydrophobic interactions Proline has an aliphatic side chain with a distinctive cyclic structure. The secondary amino (imino) group of proline residues is held in a rigid conformation that reduces the structural flexibility of polypeptide regions containing proline

12. Ramachandran Map The highly occupied areas of these plots have a good correspondence with low energy conformation of amino acid residues

13. Helices Protein helices are stabilized by hydrogen bonds between the amino and carboxyl groups of the amino acid residue main chains: i, i + 3 (3.10-helix) i, i + 4 (a-helix) i, i + 5 (a-helix) The average length of the a-helix is about 10–11 residues, which is approximately 17A ˚ , or three helical turns The main chain angles in the a-helix are approximately phi = psi = -60 ˚ Ala, Glu, Leu, and Met are often found Pro, Gly, Ser, Thr, and Val occur relatively rarely 3.10-helix equal approximately -60 ˚ and -30 ˚

14. Helices Proline mainly occurs in the first turn of an a-helix because it can not donate a hydrogen bond in the middle of a helix, and it creates sterical problems in a-helical conformation In a regular a-helix, all dipoles formed by the N-H .. . O-C main chain groups point along the helical axis The a-helix is stabilized by the gain of hydrophobic energy when nonpolar side chains of amino acids are shielded from the solvent According to Chothia (1976), when an a-helix is formed, the energy goes down by 2–3 kcal/mol per residue

15. Helices Most a-helices are immersed into protein interior from one side and form an exterior protein surface from the other side Analysis has shown that nonpolar residues are usually located on one side of a-helix (forming a hydrophobic cluster) and polar and charged residues are on the other side 3.10-helical conformation is relatively common in proteins. The 3.10-helix contains 3 residues and 10 main chain atoms per turn

16. Helices with internal hydrogen bonds in proteins (A) 3.10-helix; (B) a-helix.

17. Beta Strands About 36 percent of amino acid residues in globular proteins are in b-state The phi and psi main chain angles of the b-structure are spread widely in the upper left corner of the Ramachandran plot Phi = Psi = 180 ˚ corresponds to the allowed conformation and represents the fully extended conformation of the polypeptide chain When looking along the polypeptide framework, one can see that the neighboring side chain groups are pointing to the opposite directions However, such fully extended conformation is favorable for polyglycine only . In the presence of other amino acids, the phi and psi angles are slightly different

18. Beta Strands Maximum H bonding between the C=O and N-H groups of the main chain . There are two possible mutual arrangements of b strands in the b-sheet with respect to polypeptide chain direction: parallel and antiparallel Turns 60 ° per two residues The twist in b structure allows for conformational stabilization, providing energetically favorable contacts between the side chains of neighboring b-strands and the optimal orientation of the hydrogen bonds Val, Ile, Tyr, and Thr -Mostly preferred Glu, Gln, Lys, Asp, Pro, and Cys -Rarely found

19. Beta Strands (A) b-strand geometry; (B) Interacting b-strands

20. (A) Antiparallel b-sheet; (B) Parallel b-sheet Beta Strands

21. Beta Strands : A more clear picture

22. Beta Turns b-turn accounts for nearly 32 percent of all amino acid residues b-turn is a polypeptide fragment comprised of four consecutive amino acid residues in a region where the polypeptide chain changes direction roughly 180 ° b-turns are usually located on the protein surface and contain many polar and charged amino acid side chains Most turns contain glycine in the second or third position, where the absence of a side chain in glycine is favorable for the interaction among main chain atoms Proline often occurs at the second position of turns. About two-thirds of Pro-Gly and Pro-Asp sequences in proteins with known 3D structures are located in the two middle residues of b-turns Many b-turns connect neighboring fragments of secondary structures (a-a, a-b, and b-b)

23. Beta Turns

24. Thank You For Your Attention !!!