For more see > Structure
A protein has three structures -- sometimes, when combined with another protein, even four.
- The primary structure is the amino acid sequence. The amino acid sequence is what identifies each protein.
- The secondary structure is determined by the helixes, sheets, and loops that occur in different parts of the protein.
- The tertiary structure is the overall three-dimensional shape of the protein. Finding a good tertiary structure is the major goal of Foldit.
- The quaternary structure is multiple polypeptide units interacting. In Foldit, symmetry puzzles work with the quaternary shape formed when multiple copies of a protein bond with each other.
Primary Structure (PS)Edit
Primary structure determined by the sequence of amino acids making up the backbone, not the shape or position of the backbone.
Secondary Structure (SS)Edit
Secondary structure the backbone's spatial arrangements, Alpha Helix, and Beta Sheets that define the shape of the backbone. These are held in shape by hydrogen bonds. This does not include loops, because the shapes of the loops are not defined. Super Secondary Strucure (SSS) is a cluster or pattern in SS (bAb unit)
Tertiary Structure (TS)Edit
Tertiary sturcture is the position of the protein's amino acid sidechains and the hydrogen bonds that holds the protein together into a completed unit.
The structure of the whole protein forms the isosurface.
Spatial interaction as whole. Change any of the first three structures, and you will change the isosurface.
Quaternary Structure (QS)Edit
Quarternary sturcture is the outside shape of a native protein's isosurface, and how closely it fits into another protein's isosurface. This is how many different whole protein sub-units fit together, like puzzle pieces, into larger micro structures. We see this on foldit in Docking, Interface, and Symmetric puzzles, where smaller sub-unit proteins snuggle up close together forming larger structures. Fits like a key in a lock. Multiple polypeptide chain, subunit interaction.
Secondary Structures of the Protein.Edit
For more see > Secondary Structure
Helix (alpha helix)Edit
For more see > Helix
The helix (alpha helix) structure has the following characteristics:
- Rod-like structure
- 3.6 amino acids per turn
- Hydrogen bond (N-H- - -O=C)
- 4 residue ahead (n + 4)
- 1.5 Å translation
- 100 degrees
- Pitch: 54 degree
- Average size between 40 to +1000 Å (100nm or 0.1um)
A Helix with a twist, right or left?
When you look at a helix from the end and the top twist to the left, it is a "S" left hand twist helix. A "Z" right hand twist helix well twist to the right at the top when viewed from the end. A "Z" twist helix is happy helix, and a "S" twist helix is a very un-happy helix.
Rope and twine making include both "Z" right hand twist strands and a gentler "S" left hand twist to all the bundles of those strands. Both "Z" and "S" twists are essential to stabilize the torsional forces produced on a rope when it is stretched. This is the same when forming biological assemblies into larger strands. So the smaller strands are twisted one way, usualy "Z", and the bigger bundles are twisted more gently the other "S" way . Ropes need both "S" and "Z" twists to be stable otherwise if all the strands in a rope or biological structure were all "S" or "Z" twisted, the rope or strand will simply fall apart when pulled on. DNA is triple twisted into very tight compact strands. However unlike biological structures lightbulb filaments are triple-twisted helixes; but being made of a flat ribbon of tungsten metal, all the helixes twist the same way around.
Sheet (beta sheet)Edit
For more see > Sheet
The sheet (beta sheet) structure has the following characteristics:
- Flat "lightning bolt" or "zig-zag" structure with "pleats"
- Hydrogen bond (N-H- - -O=C)
- Same polypeptide chain
- Parallel or non-parallel
Roman lock form for sheet orderEdit
4u-3d-1d-2u-5d-6u where u=up and d=down
This is where the protein strand loops back and forth on itself when making a joining array of sheets. Think of a bear's claw pastry like a set of letter Cs all nested together, looping back and forth with the arms being sheets linked by hydrogen bonds all together with long loops going back and forth at the top.
Anti-parallel & Parallel - sheet formsEdit
Parallel and anti-parallel refer to the order of the segments in sheets and helices. This order is particularly important for sheets.
The most common order for bonded sheets is anti-parallel. Meaning that the segment numbers count up down up down. On parallel sheets, the segment mumbers go up up or down down. On the contact map, anti-parallel sheets form lines of squares that go from upper left down to lower right. Parallel sheets form a line of squares going the other way from upper right to lower left.
B-Turns or U-TurnsEdit
- Hair-pin or u-turn structure
Sometimes there are reactive centers that are on the outside of a protein. These may be orange sidechains with yellow balls. The yellow balls indicate that these are exposed hydrophobic side chains. Normally you would want these to be turned inward for a better score.
For more see > Amino Acids
AA (Amino Acid) = The molecular unit in the polypeptide chain. An individual amino acid is made of a carbonyl and amine group attached to a central tertiary carbon that has either an additional hydrogen atom or arrays of extended sidechain. Some acidic some basic, some polar some non-polar. Some steric. Some aromatic.
Each amino acid has its different configuration. It may vary in its polarity (which attracts water and other polar solvents), its length (stericity), its capabilities for hydrogen bonding, and its aromatic features.
Certain amino acids have a physical structures that make them best for certain features of the protein. For example:
- Leucine zipper - that form bonds between 2 parallel helices.
- Glycine hinge - forms the bend or u turn in loops at the end of the sheets.
Amino acids found in the interior or core of a protein tend to have sidechains that are non-polar. For example:
- Myoglobin - the oxygen-carrying protein in red blood cells has an interior that consists almost entirely of nonpolar residues such as leucine, valine, methionine, and phenylalanine.
Certain amino acids are found more in certain areas of the protein. For example:
- Proline is found at the bends of folded proteins
- Valine, leucine and isoleucine are hydrophobic
- Phenylalanine and trypophan are highly hydrophobic
- Hydrogen donors: tryptophan and arginine
- Hydrogen donor and acceptor: Asparagine, glutamine, serine, and threonine
- pH-dependent hydrogen donor or acceptor: glutamate, tyrosine, and histidine
Different types of sidechainsEdit
- Aliphatic sidechains: alanine, valine, leucine, glycine, proline, isoleucine
- Hydroxyl aliphatic: serine, threonine
- Aromatic sidechains: phenylalanine, tryptophan, tyrosine
- Basic sidechains: lysine, histidine, arginine
- Acidic sidechains: gltuamate, aspartate
- Amide sidechains: arginine, glutamine
- Sulfur sidechains: cysteine, methionine
In the polypeptide chain, the rotation between alpha carbon and nitrogen in the backbone is called phi (greek letter Φ), and the rotation between alpha carbon and carbonyl carbon is called psi (greek letter Ψ).
Steric hindrance, or clashes, prevent certain angles. These can be seen on the Ramachandran plot.
For more see > Amino Acids
- how do protein structures form and why. Let's consider aromacity, hydrogen bonds, steric hindrance, hydrophobicity, disulfide bridge.
Aromatics - Aromacity (delocalized pi-bond)Edit
Pi-system cluster amongst themselves.
Amino Acids start with the amino terminal, not the carboxyl terminal.
How pH can affect amino acidsEdit
Amino acids with amine (hydrogen donor) or carbonyl (hydrogen acceptor)
Amino acids work as zwitterions. Zwitterions are dipolar molecules. In this case, the dipolarity is found in the carbonyl (negative) and amine (positive) functional group.
For more see > Disulfide Bridge
A disulfide bridge is a covalent bond between the two sulfur atoms on each cysteine. The thiol funtional group merges together and a H2 molecule is evolved from the reaction. What was S-H H-S become S-S + H-H.
This added bond helps stabilize the structure of a protein. Not all proteins use their cysteines for this purpose, but it should be well taken into consideration.
"Intracellular proteins usually lack disulfide bonds, whereas extracellular proteins often contain several."
Chemical bond typesEdit
A covalent bond is a bond in which 2 atoms are sharing pairs of electrons. the strength of covalent bonds differs, but in general they are stronger than hydrogen bonds, van der waals, and static forces.
There are two types of covalent bonds found in proteins.
The regular covalent bond links each peptide in the polypeptide chain of the protein, and all the bonds within the amino acids.
The other type of covalent bondis found between two cysteines' sulfur atoms: a disulfide bond. Disulfide are an analog of dioxygen (peroxides) which are known for their weak bonds and are used in chemistry for free-radical reactions.
For more see > Hydrogen bond
A hydrogen bond occurs when two "heavy" atoms are sharing a hydrogen atom.
For example, in helices and sheets, the oxygen atom of a carbonyl group will be the hydrogen acceptor and the nitrogen of the amine group will be the hydrogen donor.
The dipole force is interesting for the "shape" of the hydrogen interaction. Since oxygen has 2 free electron pairs, it can accept 2 hydrogen for HB. Nitrogen has 1 free pair.Stronger than the regular dipole movement, but weaker than Covalent and Static, being only ~10% as strong as covalent bonds.
Steric hindrance, Stericity, Van der waals force = ClashesEdit
Is a force of great repulsion when 2 atoms get closer then 3-4 Å apart. This is caused by an overlap of their electron clouds or isosurface The further away, the weaker the force.
Carbon to oxygen (C-O) optimal distance = 3.4 Å, which is the the radii of both (1.4 and 2.0 Å). Only about ~1Kcal/mol.
Low compared to hydrogen bonds. Which compares to the average thermal energy of molecules at room temperature ~0.6Kcal/mol
Bigger atoms have a larger dispersion force (London force).
Temporary fluctuating dipolesEdit
Polarity or Electrostatic bondEdit
Ionic bond, salt linkage, salt bridge, ion pair Polar amino acids tend to attract water as water is polar. These tend to be on the outside of the protein.
- Disulfide Bridge
- Glycine Hinge
- Hydrogen bond
- Steric hindrance: see wikipedia article Steric Effects
- wikipedia article Aromatic Interaction
- Hinge prediction - stonehinge
- Hinge prediction - HingeMaster Server and Database
- Hinge prediction - rigidfinder
- Protein motion - molmovdb
- Protein motion - molmovdb "gallery of morphs"
For more tips and tricks see > The Foldit Labs