CS790 – Introduction to Bioinformatics

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Oct 2, 2013 (4 years and 1 month ago)

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CS790


Bioinformatics

Protein Structure and Function

1

Review of fundamental concepts


Know how electron orbitals and subshells are
filled


Know why atoms “prefer” a specific number of
covalent bonds:

O

2


N

3


H

1

C

4


S

2


O and N tend to form hydrogen bonds, C does
not.


Symmetry and electronegativity


CS790


Bioinformatics

Protein Structure and Function

2

Fundamental concepts, cont’d


Types of molecular interactions


Covalent


polar


ionic


Hydrogen bonds


Van der Waals interactions


Concentraction: moles/liter


Acids and bases


pH =

log[
H
+
]


pH = pKa : protonated/unprotonated species at equilibrium


pH < pKa : more protonated


pH > pKa : less protonated

CS790


Bioinformatics

The Structure and

Functions of Proteins

CS 790


Bioinformatics

CS790


Bioinformatics

Protein Structure and Function

4

Proteins are chains of amino acids


Polymer



a molecule composed of repeating units

CS790


Bioinformatics

Protein Structure and Function

5

Amino acid composition


Basic Amino Acid

Structure:


The side chain, R,

varies for each of

the 20 amino acids


C

R

C


H

N

O

OH

H

H

Amino

group

Carboxyl

group

Side chain

CS790


Bioinformatics

Protein Structure and Function

6

The Peptide Bond


Dehydration synthesis


Repeating backbone: N

C



C

N

C



C



Convention


start at
amino terminus

and proceed
to
carboxy terminus

O

O

CS790


Bioinformatics

Protein Structure and Function

7

Peptidyl polymers


A few amino acids in a chain are called a
polypeptide
. A
protein

is usually composed of
50 to 400+ amino acids.


Since part of the amino acid is lost during
dehydration synthesis, we call the units of a
protein
amino acid
residues
.

carbonyl

carbon

amide

nitrogen

CS790


Bioinformatics

Protein Structure and Function

8

Side chain properties


Recall that the electronegativity of carbon is at
about the middle of the scale for light elements


Carbon does not make hydrogen bonds with water
easily


hydrophobic


O and N are generally more likely than C to h
-
bond
to water


hydrophilic


We group the amino acids into three general
groups:


Hydrophobic


Charged (positive/basic & negative/acidic)


Polar

CS790


Bioinformatics

Protein Structure and Function

9

The Hydrophobic Amino Acids

Proline severely

limits allowable

conformations!

CS790


Bioinformatics

Protein Structure and Function

10

The Charged Amino Acids

CS790


Bioinformatics

Protein Structure and Function

11

The Polar Amino Acids

CS790


Bioinformatics

Protein Structure and Function

12

More Polar Amino Acids

And then there’s…

CS790


Bioinformatics

Protein Structure and Function

13

Planarity of the peptide bond

Phi (

)


the
angle of
rotation about
the N
-
C


bond.

Psi (

)


the
angle of
rotation about
the C

-
C bond.

The planar bond angles and bond
lengths are fixed
.

CS790


Bioinformatics

Protein Structure and Function

14

Phi and psi




=


= 180
°

is
extended
conformation




: C


to N

H




: C=O to C


C


C=O

N

H

CS790


Bioinformatics

Protein Structure and Function

15

The Ramachandran Plot


G. N. Ramachandran


first calculations of
sterically

allowed regions of phi and psi


Note the structural importance of glycine

Observed

(non
-
glycine)

Observed

(glycine)

Calculated

CS790


Bioinformatics

Protein Structure and Function

16

Primary & Secondary Structure


Primary structure

= the linear
sequence

of
amino acids comprising a protein:


AGVGTVPMTAYGNDIQYYGQVT…


Secondary structure


Regular patterns of hydrogen bonding in proteins
result in two patterns that emerge in nearly every
protein structure known: the

-
helix

and the


-
sheet


The location of
direction of these periodic,
repeating structures is known as the
secondary
structure

of the protein

CS790


Bioinformatics

Protein Structure and Function

17

The alpha helix











60
°

CS790


Bioinformatics

Protein Structure and Function

18

Properties of the alpha helix











60
°


Hydrogen bonds

between C=O of

residue
n
, and

NH of residue

n
+4


3.6 residues/turn


1.5
Å/residue rise


100
°
/residue turn

CS790


Bioinformatics

Protein Structure and Function

19

Properties of

-
helices


4


40+ residues in length


Often
amphipathic

or “dual
-
natured”


Half hydrophobic and half hydrophilic


Mostly when surface
-
exposed


If we examine many

-
helices,

we find trends…


Helix formers: Ala, Glu, Leu,

Met


Helix breakers: Pro, Gly, Tyr,

Ser

CS790


Bioinformatics

Protein Structure and Function

20

The beta strand (& sheet)







135
°





+
135
°

CS790


Bioinformatics

Protein Structure and Function

21

Properties of beta sheets


Formed of stretches of 5
-
10 residues in
extended conformation


Pleated



each C


a bit

above or below the previous


Parallel/aniparallel
,

contiguous/non
-
contiguous

CS790


Bioinformatics

Protein Structure and Function

22

Parallel and anti
-
parallel

-
sheets


Anti
-
parallel is slightly energetically favored

Anti
-
parallel

Parallel

CS790


Bioinformatics

Protein Structure and Function

23

Turns and Loops


Secondary structure elements are connected by
regions of
turns

and
loops


Turns


short regions

of non
-

, non
-


conformation



Loops


larger stretches with no secondary
structure. Often disordered.


“Random coil”


Sequences vary much more than secondary
structure regions

Levels of Protein
Structure


Secondary structure
elements combine to
form tertiary structure


Quaternary structure
occurs in multienzyme
complexes


Many proteins are
active only as
homodimers,
homotetramers, etc.

CS790


Bioinformatics

Protein Structure and Function

25

Protein Structure Examples

CS790


Bioinformatics

Protein Structure and Function

26

Views of a protein

Wireframe

Ball and stick

CS790


Bioinformatics

Protein Structure and Function

27

Views of a protein

Spacefill

Cartoon

CPK colors

Carbon =
green, black,
or grey

Nitrogen =
blue

Oxygen = red

Sulfur =
yellow

Hydrogen =
white