Molecules of Life Shekhar C. Mande

1. Molecules of Life Shekhar C. Mande

3. C, H, N, O, S & P make up >99% of cellular weight Composition of Cells

4. Water distribution on the Earth

6. + - As water transpires off the leaves the cohesion pulls more water up through the vessels. Basic properties of water: Because of the unequal distribution of charge, water molecules attract each other, and that is the reason why they form drops!

7. Basic properties of water: • It is the only natural substance which is found in all the three states- gas, liquid and solid at the temperatures normally found on the earth.

8. Basic properties of water: • Anomalous properties enormously important in maintaining the ecosystem of the Earth.

9. Basic properties of water: • It has very high surface tension- also the molecular basis of capillary action= allows through roots of plants, and tiny blood vessles • T = surface tension (J/m² or N/m) • θ = contact angle • ρ = density of liquid (kg/m3) • g = acceleration due to gravity (m/s²) • r = radius of tube (m) For a 1m wide tube, the water would rise a unnoticable 0.014mm. However, for a 1cm wide tube, the water would rise 1.4mm, and for a capillary tube with radius 0.1mm, the water would rise 14cm, or around 6 inches.

10. Basic properties of water: Water has high heat of vaporization: the amount of heat needed to turn a given amount of liquid water into water vapour (gas). A high heat vaporization means that in order for water to reach the gaseous state, it must absorb a great deal of heat from the surroundings. For many plants and animals, this property is the basis of a natural cooling system. Water evaporating from leaves, skin or lungs uses up heat from the organisms in the process of changing from liquid to gas. That is the reason mammals have evolved sweat glands, when the body is overheated, the glands pour watery "sweat" onto the skin, as the water evaporated, large amounts of body heat are used up and the body is cooled.

11. Basic properties of water: • Has high specific heat index= it can absorb lot of heat before it starts getting hot. Due to it high specific heat, water is slow to undergo changes in temperature. Much heat must be added or removed before the temperature of water changes much. The temperature of the water within living organisms tends to change more slowly than does that of the surrounding air or soil, so that the living cells are buffered somewhat against temperature fluctuations. This kind of protection is important because many biochemical reactions will take place only within a narrow range of temperatures.

12. Miller Urey Experiment • 1953, starting material CH3, NH3, H2 and H2O • Compounds observed included nucleotide bases and amino acids

13. Combinations of four types methyl (-CH3), hydroxyl (-OH), carboxyl (-COOH) and amino (-NH3) Four different types of molecular building blocks: Biomolecular Building Blocks

14. Sugars They are important metabolically. Sugars are the major energy storage molecules for living organisms. Their carbon rings contain large amounts of energy C6H12O6 6CO2 + 6H2O releases 686 Kcal/mol Glucose Fructose Ribose Deoxyribose

15. Cell Membrane Protects cellular components from diffusing into external environment • Membrane components may: • be protective • regulate transport in and out of cell or subcellular domain • allow selective receptivity and signal transduction by providing transmembrane receptors that bind signaling molecules • allow cell recognition • provide anchoring sites for cytoskeletal filaments or components of the extracellular matrix. This allows the cell to maintain its shape and perhaps move to distant sites. • help compartmentalize subcellular domains or microdomains • provide a stable site for the binding and catalysis of enzymes. • regulate the fusion of the membrane with other membranes in the cell via specialized junctions ) • provide a passageway across the membrane for certain molecules, such as in gap junctions. • allow directed cell or organelle motility

16. Membrane lipids Choline Phosphate Glycerol Fatty acid • Phospholipids are the principal lipids in cell membranes • They contain polar head group and hydrophobic tail

17. Nucleotides

18. Bases

19. Amino Acids Genetic code specifies 20 different amino acids CH3

20. R R C C H H N CO CO N Chirality of Amino Acids L- form D- form

21. Primary structure Un-branched polymer 20 side chains (residues or amino acids) Higher order structures Secondary: local (consecutive) in sequence Tertiary: 3D fold of one polypeptide chain Quaternary: Chains packing together Protein Structures

22. Primary Structure

23. Proteins consist of amino acids linked by peptide bonds Each amino acid consists of: a central carbon atom an amino group a carboxyl group and a side chain Differences in side chains distinguish the various amino acids Protein Architecture

24. Amino Acids and Their Symbols

25. Hydrophobic Ala, Val, Leu, Ile, Phe, Pro, Met Charged Arg, Asp, Glu, Lys Polar Ser, Thr, Tyr, Asn, Gln, His, Cys, Trp Properties of 20 amino acids

26. Convention of Naming Side Chain Atoms

27. Polypeptide Chain

28. Properties of Amino Acids • Glycine increases main chain flexibility. • Symmetry at the Ca atom • Can adopt many different conformations • Evolutionarily conserved • Occurs in tight turns

29. Properties of Amino Acids • Alanine is smallish non-polar residue • Occurs abundantly • No preference for inside or surface of the protein

30. Properties of Amino Acids • Val, Leu and Ile are branched side chains • Branching allows limited internal flexibility • Occur primarily in protein cores • “Bricks” around which functional parts are assembled

31. Properties of Amino Acids • Phe, Tyr and Trp are the aromatic side chains • All these contain one methylene group as a spacer • Side chain flexibility is restricted • Occur predominantly in the core of proteins • Tyr can form strong H-bond with its -OH group

32. Properties of Amino Acids • Met and Cys are the sulfur containing side chains • Met is rather large and flexible • Met occurs predominantly inside the core • Cys is special: it can form disulfide crosslinks and is polar

33. Properties of Amino Acids • Asn and Gln have amide in side chain • Gln has an extra methylene group, rendering the polar group flexible and reducing its interaction with main chain • H- bond donor as well as acceptor

34. Properties of Amino Acids • Asp and Glu are -vely charged at physiological pH • Althoughly chemically similar, markedly different effect on the conformation and chemical reactivity • Asp relatively rigid, and found frequently in active sites • Mostly found on protein surfaces • Can be effective chelators of metal ions

35. Properties of Amino Acids • Lys and Arg are +vely charged residues • Long and flexible • Can form salt bridges or help in catalysis

36. Properties of Amino Acids • Ser and Thr are small and aliphatic • -OH no more reactive than ethanol • Frequently form H-bond with main chain

37. Properties of Amino Acids • Pro is imino acid • Reduces main chain flexibility drastically due to cyclization • Can often occur in cis- form

38. Properties of Amino Acids • His is a very special residue with pKa of 6.0 • Can be uncharged or charged easily • Very suitable for catalysis, found in most active centres

39. Chemical Similarity Reflects in Substitution Matrices

40. Hydrophobicities

41. NAME EIS KD WHI ALA 0.62 1.80 -0.50 ARG -2.53 -4.50 -1.81 ASN -0.78 -3.50 -0.85 ASP -0.90 -3.50 -3.64 CYS 0.29 2.50 0.02 GLN -0.85 -3.50 -0.77 GLU -0.74 -3.50 -3.63 GLY 0.48 -0.40 -1.15 HIS -0.40 -3.20 -2.33 ILE 1.38 4.50 1.12 LEU 1.06 3.80 1.25 LYS -1.50 -3.90 -2.80 MET 0.64 1.90 0.67 PHE 1.19 2.80 1.71 PRO 0.12 -1.60 -0.14 SER -0.18 -0.80 -0.46 THR -0.05 -0.70 -0.25 TRP 0.81 -0.90 2.09 TYR 0.26 -1.30 0.71 VAL 1.08 4.20 0.46 Comparison of Kyte-Doolittle, Eisenberg and White Scales

42. Peptide torsion angles

43. Some mostly beta architectures

44. The Protein Folding Problem