ICM-Introductionx

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4 Οκτ 2013 (πριν από 3 χρόνια και 10 μήνες)

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Overview of Key ICM Features

NIBR
-

Emeryville

July 10
-
11 2012

Introduction to
MolSoft


Established in 1994


Privately owned


Worldwide customer
base in academia,
pharma

and biotech


Many published success
stories in comp bio &
chem


Support

E
-
mail

andy@molsoft.com

support@molsoft.com

Call:

858
-
625
-
2000 x108

www.molsoft.com/news.html

Molecule Visualization


Store in a single file:


Representations


Lighting/Depth


Multiple Slides


Multiple Viewpoints


Annotation


Rendering


Parametric Animations


Alignments


Chemical Tables

Product: ICM
-
Browser &
ActiveICM

iMolview

for the
iPad

and
iPhone

Bioinformatics


Fully interactive
alignments


Trees


Sequence and
alignments directly
linked to 3D structure


Rich alignment editor


Sequence search PDB,
Uniprot

etc…

Structure Analysis


Calculate


RMSD


Contact Areas


Surface Areas


Measure distances and
angles (planar, dihedral)


Fully interactive
Ramachandran

Plots


Protein Superposition

Structure Prediction


Identify closed cavities


Identify
ligand

binding
sites (An et al 2005 &
Kufareva

et al 2012)


Identify protein
-
protein
interaction sites
(Fernandez
-
Recio

et al
2005)


Protein health

An,

J
.
,

Totrov
,

M
.
,

and

Abagyan
,

R
.

(
2005
)
.

Pocketome

Via

Comprehensive

Identification

and

Classification

of

Ligand

Binding

Envelopes
.

Mol

Cell

Proteomics

4
,

752

761
.


Kufareva

I,

Ilatovskiy

AV,

Abagyan

R
.

Pocketome
:

an

encyclopedia

of

small
-
molecule

binding

sites

in

4
D
.

Nucleic

Acids

Res
.

2012

Jan
;
40
(Database

issue)
:
D
535
-
40
.


Fernandez
-
Recio

J,

Totrov

M,

Skorodumov

C,

Abagyan

R
.

Optimal

docking

area
:

a

new

method

for

predicting

protein
-
protein

interaction

sites
.

Proteins
.

2005

Jan

1
;
58
(
1
)
:
134
-
43


Crystallographic Analysis


Neighbors


Cell


Biomolecule

generator


Display and contour
electron density maps

Homology Modeling


Build homology models
(
Katritch

et al 2010)


Refine models


Predict and/or design
loop conformation


Search loop databases


New loop modeling
force
-
field (
Arnautova

et al 2011)

Arnautova

YA,
Abagyan

RA,
Totrov

M. Development of a new physics
-
based internal coordinate mechanics force field and its application to
protein loop modeling. Proteins. 2011 Feb;79(2):477
-
98.



Katritch

V,
Rueda

M, Lam PC, Yeager M,
Abagyan

R. GPCR 3D
homology models for
ligand

screening: lessons learned from blind
predictions of adenosine A2a receptor complex. Proteins. 2010
Jan;78(1):197
-
211

3D Interactive
Ligand

Editor


Interactively edit a
ligand

bound
to a receptor in 3D.


Screen for best replacement
group


Join fragments by linkers.


Edit
ligand

in 2D molecular editor.


Delete atoms and bonds.


Convenient undo and redo
modification feature.


Dock and/or minimize edited
ligand
.


Fragment docking.


Multiple receptor docking


Restrain atoms during docking


Cheminformatics


2D
ligand

sketcher


Fully interactive
chemical spreadsheets
and plots


Chemical clustering


Chemical searching


Library enumeration


Pharmacophore

searching



Atomic Property Fields

A continuous, multi
-
component 3D
potential that reflects preferences
for various atomic properties at
each point in space.

Totrov

M.
Ligand

binding site superposition and comparison
based on Atomic Property Fields: identification of distant
homologues, convergent evolution and PDB
-
wide clustering of
binding sites. BMC Bioinformatics. 2011 Feb 15;12
Suppl

1:S35.


Grigoryan

AV,
Kufareva

I,
Totrov

M,
Abagyan

RA. Spatial
chemical distance based on atomic property fields. J
Comput

Aided Mol Des. 2010 Mar;24(3):173
-
82.


Totrov

M. Atomic property fields: generalized 3D
pharmacophoric

potential for automated
ligand

superposition,
pharmacophore

elucidation and 3D QSAR.
Chem

Biol

Drug
Des. 2008 Jan;71(1):15
-
27.


Docking & Screening


Small molecule docking


Protein
-
protein docking


Template docking


Induced Fit Docking


Multiple Receptors


Explicit Groups


Tethered Docking


Virtual Screening


Structure
-
based


Ligand
-

based APF


See:
www.molsoft.com/vls

for success stories

ICMDB


What is it?


A single,
unified
client for data
entry, mining and manipulation
built into a
powerful chemistry
and
bio
-
enabled platform



Prerequisites


One
or multiple
(possibly
existing)
relational databases
with research data related to
biology and
chemistry



Deployment


A cross
-
platform client


Installs transparently on
top of
existing databases