hotspot wizard - What If

thelemicbathBiotechnology

Feb 20, 2013 (4 years and 5 months ago)

129 views

Los c hmi dt

La bor a t or i e s

Ena nt i s
, Lt d
.

PROTEI N ENGI NEERI NG

LOSCHMI DT LABORATORI ES
& ENANTI S


1 7 ye a r s e x p e r i e n c e i n
p r o t e i n s c i e n c e


mu l t i
-
d i s c i p l i n a r y

t e a m

LOSCHMI DT LABORATORI ES
& ENANTI S


1 7 ye a r s e x p e r i e n c e i n
p r o t e i n s c i e n c e


mu l t i
-
d i s c i p l i n a r y

t e a m


l a b o r a t o r i e s a n d f a c i l i t i e s

( 1.5 mi l E U R )

Un i v e r s i t y
Ca mp u s

a n d

Bi o t e c h n o l o g y
I n c u b a t o r
, Br n o

LOSCHMI DT LABORATORI ES
& ENANTI S


1 7 ye a r s e x p e r i e n c e i n
p r o t e i n s c i e n c e


mu l t i
-
d i s c i p l i n a r y

t e a m


l a b o r a t o r i e s a n d
f a c i l i t i e
s

( 1.5 mi l E U R )

Un i v e r s i t y
Ca mp u s

a n d

Bi o t e c h n o l o g y
I n c u b a t o r
, Br n o


mo l e
c
u l
a r

b i o l o g
y

a
n d

mi
c
r o b i o l og
y

LOSCHMI DT LABORATORI ES
& ENANTI S


1 7 ye a r s e x p e r i e n c e i n
p r o t e i n s c i e n c e


mu l t i
-
d i s c i p l i n a r y

t e a m


l a b o r a t o r i e s a n d
f a c i l i t i e
s

( 1.5 mi l E U R )

Un i v e r s i t y
Ca mp u s

a n d

Bi o t e c h n o l o g y
I n c u b a t o r
, Br n o


mo l e
c
u l
a r

b i o l o g
y

a
n d

mi
c
r o b i o l og
y


b i o i n f o r ma t i c s

a
n d

mo l e c u l a r

mo d e l l i n g


1 7 ye a r s e x p e r i e n c e i n
p r o t e i n s c i e n c e


mu l t i
-
d i s c i p l i n a r y

t e a m


l a b o r a t o r i e s a n d
f a c i l i t i e
s

( 1.5 mi l E U R )

Un i v e r s i t y
Ca mp u s

a n d

Bi o t e c h n o l o g y
I n c u b a t o r
, Br n o


mo l e
c
u l
a r

b i o l o g
y

a
n d

mi
c
r o b i o l og
y


b i o i n f o r ma t i c s

a
n d

mo l e c u l a r

mo d e l l i n g


b i o c h e mi s t r y

a n d

b i o p h ys i c s

LOSCHMI DT LABORATORI ES
& ENANTI S

LOSCHMI DT LABORATORI ES
& ENANTI S

BI OSENSI NG

DECONTAMI NAT I ON

BI OCATALYSI S

DEVELOPMENT OF BI OCATALYTI C PROCESS


GENE
T I C

DATABASES


EXT REMO
PHI L ES

DEVELOPMENT OF BI OCATALYTI C PROCESS


DI RECT ED EVOL UT I ON


r e s i s t a n c e t o o r g a n i c

s o l v e n t s

DEVELOPMENT OF BI OCATALYTI C PROCESS


DI RECT ED EVOL UT I ON


RAT I ONAL DESI GN


t h e r mo s t a b i l i t y

e n h a n c e me n t

DEVELOPMENT OF BI OCATALYTI C PROCESS


DI RECT ED EVOL UT I ON


RAT I ONAL DESI GN


t h e r mo s t a b i l i t y

e n h a n c e me n t

DEVELOPMENT OF BI OCATALYTI C PROCESS


DI RECT ED EVOL UT I ON


RAT I ONAL DESI GN


t h e r mo s t a b i l i t y

e n h a n c e me n t

0
0.2
0.4
0.6
0.8
1
1.2
30
40
50
60
70
80
Native structure
Temperature [
°
C]
2 0
°
C

DEVELOPMENT OF BI OCATALYTI C PROCESS


O
PT I MI Z ED EXPRESSI ON


F ERMENTAT I ON


DOWN ST REAM

21.5
29.0
35.4
52.9
92.0
113.0
1
2
3
4
DhaA-LinB
DEVELOPMENT OF BI OCATALYTI C PROCESS


MEDI UM ENGI NEERI NG


I MMOBI L I SAT I ON

DEVELOPMENT OF BI OCATALYTI C PROCESS

HOTSPOT WIZARD

Hot Spot

Wizard

RCSB PDB

u
ser

Hot Spot

Wizard

RCSB PDB

CSA

UniProt

user

PDBSWS

HOTSPOT WIZARD

Hot Spot

Wizard

RCSB PDB

CSA

UniProt

u
ser

CAVER

CASTp

PDBSWS

HOTSPOT WIZARD

Hot Spot

Wizard

RCSB PDB

CSA

UniProt

u
ser

CAVER

CASTp

PDBSWS

tunnels

Cd
-
hit

BLA
ST

NR
DB

MUSC
LE

Rate
4Site

HOTSPOT WIZARD


low


high

mutabilit
y

HOTSPOT WIZARD

1,3
-
1,4
-
b
-
glucanase


PDB
-
ID 1GBG

haloalkane

dehalogenase

PDB
-
ID 1
BN6


p
hosphotriesterase

PDB
-
ID 1I0D

b
-
lactamase

PDB
-
ID 1BLS

HOTSPOT WIZARD

0
0.2
0.4
0.6
0.8
1
9
8
7
6
5
4
3
2
1
+

Estimated mutability

hot spots

region

Proportion of mutations

HOTSPOT WIZARD





positive and neutral





0
0.2
0.4
0.6
0.8
1
9
8
7
6
5
4
3
2
1
Estimated mutability

hot spots

region

Proportion of mutations

HOTSPOT WIZARD





positive and neutral


slightly negative



0
0.2
0.4
0.6
0.8
1
9
8
7
6
5
4
3
2
1




positive and neutral


slightly negative


deleterious


Estimated mutability

hot spots

region

Proportion of mutations

HOTSPOT WIZARD

HOTSPOT WIZARD

Pavelka

et al.
Nucl
.
Acids

Res.

37: W376 2009