Introduction to Structural Bioinformatics

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Oct 1, 2013 (4 years and 1 month ago)

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'ב רטסמס א"עשת


Introduction to Structural Bioinformatics

Ilan Samish
&
Eran Eyal


Course book
:

Bourne P. &
Gu J. (Eds.) Structural Bioinformatics (2
nd

edition),

Wiley, 2009.


Description
:

In the last decade, the Protein Data Bank (PDB)
,

housing data on
protein structures
,

has
grow
n by an order of magnitude and biological sequence data has grown far more.
Consequently, new tools are required to analyze
the

raw data, predict the structure
-
function
relationship of available structures as well as predict the

structure of new sequences. In this
course we will introduce the tools available for
the structural bioinformaticis
t including
algorithms and
scientific
background
. Case
-
studies, e
xisting and emerging trends will be
outlined
.


Topics include
: s
tructural v
isualization, databases,

structural analysis,

structural predictions
and model building
, s
tructural classification, structural alignment, protein
-
protein and
protein
-
ligand docking

(molecular recognition)
, motion analysis,
molecular dynamics
,
disordered pr
oteins and
virtual drug design
.


Syllabus
:


1.
Introduction and overview



15.2.2011
(
ch. 1
)


A.

Introduction

B.

Structural bioinformatics and its orientation among other disciplines.

C.

Protein structure


review from a computational parameterization aspect

D.

Over
view of the course
materials

via case
-
studies: nano
-
machines,

nano
-
electronics,

HIV, Viagra and head
-
aches

.

2.
Structural
data,
databases

and datamining



22.2.2011

(
ch.
10
-
13
)

A.

PDB (history, size, content,
source of information,
quality)

B
.

PDB file form
at
. I
nformation beyond

the
coordinates
.

C.

OCA browser


the WWW interface.

D.

Basic principles of molecular
v
isualization

(molecular graphics).

E.

Overview of NDB and CSD


3
. From sequence to structure


1.3.2011

(
ch. 17, 23 and other sources
)

A.

Anal
ysis of protein

families in sequences


blocks, profiles, and their utilization in
structural modeling.

B.

Correlated mutations and their use in structure analysis
.

C.

Mapping of evolutionary data on protein structures.



4
.
Structural alignment and structural clas
sification o
f the protein world
-

8.3.2011


(
ch. 16
-
18
, 20
)

A.

The super
position a
nd structural alignment problem
.

B.

Analytical methods to solve the
problem


global/local superposition vs. substrate
-
directed

superposition (SDSI), pairwise/
multiple superposition.

C.

Traditio
nal
S
trategies to solve the structural alignment problem:
double dynamic
programming (SSAP),
vector representation of secondar
y structure elements
(SARF/CE).

D.

Defining the elusive domain


full protein alignment vs. structural domain alignment.

E.

Advanced alg
orithmic approaches to the structural alignment problem: dot matrix
(Dali), geometric hashing (CA match).


F.

Classifications based on structural alignments: SCOP, CATH, FSSP


5
. Analysis of 3D structures

-

15.3.2011



(
ch.
14
-
15 and other sources
)

A. Addin
g hydrogens to structures.

A
.

Analysis of hydrogen bonds

B
.

Analysis of cavities.

C. Validity of coordinates


fixing side
-
chain flips

D
.

Analysis of atomic contacts
-

LPC/CSU.

E
.

Crystal contact analysis

F
.

Structural influences of point mutations


6
.
Structural Modeling
1



s
econdary structure prediction

in 1D space

-

22.3.2011
(
ch.
1
9, 29
and other sources
)

A.

Secondary structure assignment


automatic

vs. manual
annotation
.

B.

Introduction

to machine learning approaches.

C.

T
he PHD algorithm.

D.

Prediction of so
lvent accessible surface.

E.

Demonstration of web servers.


7
.
Structural Modeling
2



scoring functions
-

29.3.2011
(
ch. 24, 37 and other sources
)

A.

Force fields
.

B.

Know
ledge
-
based potentials

C.

Surface area based functions



8
.
Structural Modeling
3



search and
sampling



6.4.2011

(
ch. 8
)

A.

Grid search

B.

Stochastic methods


Monte Carlo algorithms

C.

Genetic algorithms

D.

biases and non
-
redundancy


9
.
Structural Modeling
4



Building comple
te models of protein structures


13.4.2011

(
ch.
28, 30
-
32
)

A.

Homology models

B.

Fold rec
ognition

C.

Ab Initio

methods

D.

Modeling side chain conformations

E.

Analysis of model credibility


software, algorithms, approach.

F.

CASP, CAFASP competitions.



10
.
Structural bioinformatics in system biology



3.5.2011

(
ch.
25
-
27
)

A.
Structural data on protein
-
protein interfaces.

B. Quaternary structure prediction

B.

Protein


Pr
otein docking
.

C.

Ligand


Protein docking (flexible
/
rigid, local
/
global). Description of

a

specific
algorithm
.



1
1
.
Molecular motions
-

17.5.2011

(
ch.
37
)

A.

Extracting dynamic information fro
m structural data.

B.

M
olecular dynamics



granularity vs. complexity
,
empirical energy function,
algorithms, simulation protocols,
treatment of solvent,
trajectory analysis,

C
.

Normal mode analysis


1
2
.
Protein design
, designability

and disordered
proteins

-

24
.5.2011

(
ch. 38, 39

and other
sources
)

A.

Design principles for functional proteins

B. Designability of natural proteins

C
. Biology and function of disordered protein

D
.

Prediction of disordered proteins


13.
Membrane Proteins

-


31.5.2011

(
ch. 36
)

A.

F
inding membrane spanning regions

B.

Unique parameterization of membrane proteins

C.

Alignment of membrane proteins within the membrane.

D.

Membrane protein protein
-
protein interactions (docking and drug design)


Drug design
(
ch.
27,
34
)

E.

Docking small molecules



from computational biology to computational chemistry.

F.

Virtual combinatorial libraries.

G.

Database screening.

H.

Incremental building.

I.

Commercial software.