Fehérjék 4
Simon István
Predicting protein disorder - IUPred
• Basic idea:
If a residue is surrounded by other residues such that
they cannot form enough favorable contacts, it will not
adopt a well defined structure
it will be disordered
• The algorithm:
…..QSDPSVEPPLSQETFSDL WKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGPDEAPRMPEAAPRVA PAPAAPTPAAPAPA…..
Amino acid
composition
of environment:
A – 10%
C – 0%
D – 12 %
E – 10 %
F–2%
etc…
Estimate the
interaction
energy between
the residue and
its sequential
environment
Decide the
probability of the
residue being
disordered based
on this
Predicting protein disorder - IUPred
• Back to p53:
Interaction energies:
Amino acid composition of the
residue D:
A – 10%
C – 0%
D – 12 %
E – 10 %
F–2%
stb…
The predicted interaction energy:
E = 1.16*0.10 +(-0.82)*0+…
=1.138 97%, that it is disordered
Predicting binding sites - ANCHOR
• 3 – Interaction with globular proteins
We consider the average amino acid composition of a
globular dataset instead of the own environment:
A – 10%
C – 0%
D – 12 %
E – 10 %
F–2%
stb…
A – 7.67%
C – 2.43%
D – 4.92 %
E – 5.43 %
F – 3.19 %
stb…
Composition
calculated on a large
globular dataset
The thus gained energy:
20
gain
Ei
 Ei
int
 E glob , i
int
where
E glob , i 
int
P
ij
j 1
f glob , j
Predicting binding sites - ANCHOR
• Example: N terminal
p53
Contains three binding
sites:
– MDM2: 17-27
– RPA70N: 33-56
– RNAPII: 45-58
P = p1*Saverage + p2*Eint + p3*Egain
Transzmembrán fehérjék
Anyagcsere folyamatok
Transzporterek
Ion csatornák
Hordozók
Információ csere
Receptorok
A transzmembrán fehérjék két formája
E. Coli klorid csatorna fehérje
Ismert szerkezetű transzmembrán fehérjék szerkezetét vizsgáló szerverek
Hidrofobicitás
Aminosav helyettesítési mátrix
Szerkezetbecslés homológia alapján
Az emberi rodopszin és a bakteriorodopszin
aminosav- sorrendjeinek összehasonlítása
A DAS szerver algoritmusa
DAS profiles of a TM protein as function of residue number
A HMMTOP algoritmus
O
o
H
i
I
 n
max   p j,s
 j= 1

 , s= I,i,H,o,O



Ismert szegmensek lokalizációja
C
Protein A
N
Intracellular
domain Q
C
Pfam
Prosite
Prints
N
Smart
Protein B
Intracellular
domain Q
Scanning
Protein C
TM selection
of UniProtKB
TOPDOM
N
Intracellular
domain Q
N
?
Intracellular
domain Q
C
?
C
Unknown
Protein