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1 INVENTUS v1.0 USER GUIDE
INVENTUSTM β v1.0
USER’s GUIDE
InventusTM
Version 1.0 Rev. β
October 2014
A product by
Novo Informatics Pvt. Ltd.
IIT-D based Company
New Delhi, India
2 INVENTUS v1.0 USER GUIDE
Copyright © 2014 Novo Informatics Pvt. Ltd., All rights reserved.
Inventus is a trademark of Novo Informatics Pvt. Ltd.
The following are either registered trademarks or trademarks of
Microsoft Corporation in the United States and/or other countries:
Microsoft Visual Studio 2010 Professional, Microsoft Excel.
pkExpress is a propertiary of G2 Research, Inc (USA)
Adobe Acrobat is a registered trademark of Adobe Systems Incorporated.
Intel Pentium is a registered trademark of Intel Corporation.
3 INVENTUS v1.0 USER GUIDE
Chapter 1
INVENTUS™ is a comprehensive software suit
developed and validated to predict relevant
computational studies like protein structure optimization,
virtual high throughput screening, docking, geometry
calculations and ADME characteristics of potential
drugs. The software can be deployed as a PC desktop
application or as a large compute engine.
INVENTUSTM
major module includes the following:
PocketDetector
HitsGen (Virtual High throughput Screening)
BioAff (Binding energy Calculator)
NovoDocker (Docking)
PharmoPredicta (ADME based model along with
sensitivity analysis)
The Need for INVENTUSTM
Historically, inappropriate calculations and accuracy in
results have been a major reason for the failure of
compounds in the later stages of drug development. This
fact was largely due to an inability to identify and rectify
right candidate as well as poor pharmacokinetic
characteristics present in many lead series accepted for
lead optimization. With the adoption of High throughput
screening, Docking & MD simulations, combinatorial
chemistry, and parallel synthesis in drug discovery, the
need for early information on the absorption,
metabolism, distribution and elimination (ADME) of a
compound has become increasingly important in the lead
selection and optimization process. This need has driven
the development of in silico models for predicting initial
hits molecules against selected targets and to
characterize the ADME characteristics of a compound at
early stages. Using this information, computational
biologist and chemists steer away complexes using
additional information from INVENTUSTM
.
The INVENTUSTM
predictive models were trained using
a diverse data set of public repository data as well as
4 INVENTUS v1.0 USER GUIDE
internally generated in vitro data, human
pharmacokinetic data from clinical trials, chemical
structure, and development successes and failures. The
models were internally and externally validated to
benchmark their performance. The following is a brief
overview of the models and capabilities of
INVENTUSTM
. For more information, see the chapters
following this introduction.
INVENTUSTM version 1.0 InventusTM is a complete drug discovery suite which
was based on the state of the art technology
developed by supercomputing facility for
bioinformatics (SCFBIO Lab) at Indian Institute of
Technology Delhi (India). InventusTM aims on
providing integrated software solutions that truly
meet its customer‟s needs. It empowers researchers
around the world to achieve the goal of improving
human health and quality of life through advanced
computational techniques which can help
experimental biologist to identify potential leads.
HitsGenTM Computational drug discovery is expensive process
in both cost and time. The prime need in the virtual
screening process is the speed and accuracy, where
speed in terms of time required in screening and
accuracy in terms of finding true positives. In nearly
all cases of virtual screening there are both false
positive and true positive in the screened compound
pool of libraries. Inventus virtual high throughput
screening is based on the protocol developed, which
was successfully able to remove false positive from
the screened molecules. Molecules can be screened
using customized library as well as embedded
library (size ~ 40mn).
The screening methodology is based on structural
and physicochemical descriptors of small molecule
and functional groups lining the active sites of
bimolecular targets, for estimating binding affinity
with significantly reduced time, facilitating a rapid
scanning of large databases in the search for hit
molecules.
5 INVENTUS v1.0 USER GUIDE
NovoDockerTM
Molecular docking is a computational procedure
that predicts the non-covalent binding of
macromolecules or, more frequently of a
macromolecule (receptor) and a small molecule
(ligand) efficiently. The key characteristic of a good
docking program is its ability to reproduce
experimental binding poses of ligand. To test this
ability the ligand is taken out of X-ray structure of
its protein-ligand complex and docked back into its
binding site. The docked binding pose was
compared with the experimental binding pose, and a
root mean square (RMSD) between the two is
calculated, if the calculated RMSD between these
two poses were under 2Å a then the prediction of
binding pose was considered as successful for a
particular protein-ligand complex.
BioAffTM
Binding energy calculation of protein-ligand
complex. Inventus binding energy employs a
computationalluy fast protocol for predicting
binding affinities of non-metallo protein-ligand
complexes.The protocol was based on a all atom
energy based empirical scoring function comprising
electrostatics, van der Waals ,hydrophobicity and
loss of conformational entropy of protein side
chains upon ligand binding
PharmoPredictaTM
Inventus pk Express has been bought from G2 Research
(US based company). The InventusTM pkEXPRESS
physiological models were trained using a diverse
data set of internally generated in vitro data, human
pharmacokinetic data from clinical trials, chemical
structure, and development successes and failures.
The models were internally and externally validated
to benchmark their performance. The following is a
brief overview of the models and capabilities of
Inventus pkEXPRESS.
6 INVENTUS v1.0 USER GUIDE
Physiological Absorption Model Developed in collaboration with five major
pharmaceutical companies, the patented (1) Absorption
Model in pkEXPRESS predicts human intestinal
absorption. The system's patented dispersed plug flow
model of absorption simulates human physiology and
accounts for the regional solubility, regional
permeability, intestinal surface area, and fluid flow in
the gastrointestinal tract. Optimized using internally
generated in vitro data, intravenous and oral
pharmacokinetic clinical data, and chemical structures,
The 67 drugs in the Absorption Model training set span
19 different therapeutic classes and include development
successes and drugs that failed clinical trials.
Compounds in the training set were selected so that a
broad range of solubility, permeability, transport
properties, and extent of absorption was represented.
Using dose, chemical structure, solubility, Caco-2
permeability, and efflux (optional input), the Absorption
Model predicts the extent of absorption, absorption rate,
mass absorbed, soluble mass, insoluble mass, and
intestinal drug concentration of potential drugs.
Physiological Metabolism Model The InventusTM
pkEXPRESS physiological Metabolism
Model was designed and validated to predict the first
pass metabolism and bioavailability (FH) of potential
drug compounds. The parallel tube liver flow model
simulates first pass metabolism using a predicted
absorption rate from the Absorption Model, protein
binding, and metabolic stability of a compound. The
Metabolism Model was optimized using a training set of
internally generated in vitro data, literature and
collaborator pharmacokinetic clinical data, and chemical
structures. The 82 data points from 61 drugs in the
Metabolism Model training set, representing 37 different
therapeutic classes, have a broad range of Km, CLint,
protein binding, and extent of metabolism. By
incorporating the Km as well as the CLint, our
physiological model accounts for the extent of
metabolism when metabolizing enzymes become
saturated. This is an important phenomenon that is often
ignored by models, especially by those making a linear
assumption. The Metabolism Model in Inventus
pkEXPRESS incorporates the Michaelis-Menten
equation to describe turnover kinetics and successfully
7 INVENTUS v1.0 USER GUIDE
predicts FH for compounds, whether they demonstrate
linear or non-linear turnover kinetics, without
overestimating first pass metabolism.
Physiological Distribution & Elimination Based on the Distribution and Elimination Model
published by Kawai, et. al. (J. Pharm and Biopharm Vol.
22 No.5 1994), the Distribution and Elimination Model
in Inventus pkEXPRESS uses published human
physiological blood flow rates and organ and tissue
volumes to predict the plasma level time curve (PLTC),
Cmax, tmax, and area under the curve (AUC) of a
compound. From the PLTC, other relevant
pharmacokinetic parameters such as Vss, CLtot and, t1/2,
for a one or two compartment micro and macro-
constants model can be calculated.
The model was trained using intravenous and oral
pharmacokinetic data from 147 published and
proprietary clinical studies. The model predicts the
distribution and elimination of potential drugs, uses
protein binding, a red blood cell partitioning ratio, and
either the predicted rate of absorption or metabolism
obtained from the Absorption and Metabolism Models
respectively.
Sensitivity Analysis Sensitivity analysis, (i.e. how sensitive FH and FDp are
to changes in the Caco-2 permeability or dose), can be
used to investigate the impact various input parameters
have on the Inventus pkEXPRESS predictions. By using
the Inventus pkEXPRESS two dimensional sensitivity
analysis, you can quickly determine the effect of
interdependencies between parameters on the outcome.
This information on parameters can help to assess which
assays are the most useful in identifying critical
properties on which to focus lead optimization resources,
or to identify compounds with ADME liabilities that are
unlikely to be overcome.
System Requirements Minimum Computer Specifications:-
Intel® Dual Core processor
2 GB RAM
Inbuilt 8MB Graphic Card
8 INVENTUS v1.0 USER GUIDE
Recommended Computer Specifications:-
Intel® i3 processor machine
4 GB RAM
500 MB graphic Card or 1gb Graphic Card(For
HD Resolutions)
Other Operation system & software’s required:-
Microsoft® Windows 7/8 Home basic/Ultimate
Adobe® Acrobat ® Reader version 5.0 or higher
Microsoft Office 2007 or higher version
Installation What you will find on the CD-ROM
The following are included on INVENTUSTM
CD-ROM
Inventus running application
Inventus pkExpress application
Associated default parameters files
The User‟s Guide in pdb format
Validation report in pdb format
Test data to verify proper installation for
PharmoPredicta only
Installation Procedure When you insert the INVENTUS CD-ROM into your
computer drive, the Install Shield Wizard should start
automatically. (If not, open Windows Explorer and
navigate to the CD-ROM. Double-click on „setup.exe‟ to
start the Install Wizard.) The Wizard will guide you
through the setup process. After installation is complete,
you will be asked to restart your computer. If you are
using trail version it will specify number of days and
once trail is finished and you wish to continue, you need
to insert license key for activating software.
Customizing your installation
By default, InventusTM
will be installed in the Program
Files directory on the drive that contains your
computer‟s operating system (typically the C drive):
C:\Windows\NovoInformatics\Inventus
If you wish to install Inventus in a different location
from the default path, select “Custom” during the
installation (Figure 1).
9 INVENTUS v1.0 USER GUIDE
Figure 1. Customizing the Installation Location
Starting Inventus
A shortcut to Inventus will be included in your Start
menu, and a shortcut icon will be placed on your
desktop:
Start the Inventus application‟s graphical user interface
by one of the following methods:
Double-click the shortcut icon on your desktop
Select:
Start – Program files – Novo Informatics –
Inventus
10 INVENTUS v1.0 USER GUIDE
Chapter 2
UNDERSTANDING INVENTUSTM
VISUAL INTERFACE
Figure 2. Inventus Virtual Interface
Interface Overview
Complete Interface of InventusTM
is divided into 3
panels. Left hand side screen displays predictive models,
Right hand side screen displays Tree (chains of proteins
along with residues numbers and atoms as well as
compound with atoms numbers); Middle panel displays
protein, protein-ligand complexes and ligand in different
visualizations. On top header, it has button tools for
performing operations such as uploading files, changing
visual formats, zoom in, zoom out, undo, redo, save
,save As, protein visualization window, ligand
11 INVENTUS v1.0 USER GUIDE
visualization window, Contrast button. On the left hand
side screen, 4 tabs are displayed (Modules, Graphs,
PDB‟s & History).
Modules: Displays list of innovative
technologies for performing task on protein,
protein-ligand complex and ligand.
Graphs: User can utilize and design different
graphs for data. Pie chart, Bar chart and Line
chart for analyzing data
PDB’s: Tab will search out available PDB‟s on
your computer which you like to upload
History: User can check which task was run in
past. Complete history can be displayed.
Input file formats
InventusTM
supports two different types of input files:-
Protein-Ligand Complex/Protein – PDB
format
Ligand – SDF or PDB format (For small
molecules)
PharmoPredictaTM
Structure model format
files:
SMILES string
SD File
CSV File
TSV File
Note1: PDB is protein data bank file. Any
protein/protein-ligand complex file can be downloaded
from Protein Data Bank Database.
Note 2: SMILE string file is the default file type for
structural information.
Tabs Functioning FILE Tab
Options under File tab:-
Open (Protein/Protein-ligand complex files)
Format: PDB for protein & complex files and
SDF for compound files (Can be used to upload
folder for multiple compounds max. 15
compounds)
12 INVENTUS v1.0 USER GUIDE
Opening protein/protein complex file
Opening ligand file
Inventus can extract multiple ligand at a time
(max 15) from folder saved on computer.
13 INVENTUS v1.0 USER GUIDE
Figure 20. Displaying multiple ligand at a time.
SAVE AS
Options under SAVE AS tab:-
Picture
(PNG ,JPEG, BMP)
F
I
L
E
14 INVENTUS v1.0 USER GUIDE
File
R
E
C
E
N
T
I
RECENT FLES
This tab helps users to open recently opened
protein files/protein-ligand complexes.
16 INVENTUS v1.0 USER GUIDE
VIEW TAB
Visual options under View tab:-
T
h
This tab helps user to visualize protein
file/protein-ligand complex file in different
visual formats
Upload protein/complex file using FILE tab
Click on view and multiple visual options will
open
Click on any visual option to see
protein/complex in different formats
Fig 3. Ball & Stick View
Fig 4. Ribbon View
17 INVENTUS v1.0 USER GUIDE
Fig 5. Sphere View Fig 6. Wireframe View
Fig 7. Cartoon View
Fig 8. Tube View
Fig 9. Strand View Fig 10. Stick View
18 INVENTUS v1.0 USER GUIDE
Tool Panel in View
Helps user to visual tool panel while visualizing
complexes in FULL SCREEN MODE
Fig 11. Using protein toolbox from toolbox under VIEW tab
19 INVENTUS v1.0 USER GUIDE
Fig 12. Using Display Panel from toolbox under VIEW tab
Display Panel
Helps user to visualize
protein/ligands/protein-ligand complex
in different forms under FULL
SCREEN MODE. Also user can switch
off protein to visualize ligand and vice
versa.
TOOLS TAB
Information
This module gives the RCSB
information about the protein file, if
the files opened is in RCSB format.
And also gives Active Site
information about the opened
protein-ligand complex file.
R
CSB Information
OUTPUT
20 INVENTUS v1.0 USER GUIDE
Active Site Information
Volume
Calculates volume of protein, ligand,
protein-ligand complex
Gives total volume, individual
volume and volume ratio.
21 INVENTUS v1.0 USER GUIDE
R
R
Radius of Gyration
Calculates radius of gyration of
protein, ligand & protein-ligand
complex.
OUTPUT
23 INVENTUS v1.0 USER GUIDE
S
u
r
Surface Area
Calculates surface area of protein
target by selecting chain
S
i
d
e
Chain Donor Acceptors
OUTPUT Return to visualize mode
OUTPUT
24 INVENTUS v1.0 USER GUIDE
Calculates side chain donor
acceptors of protein target
Secondary Structure
Calculates secondary structure
information of protein target.
S
u
p
OUTPUT
25 INVENTUS v1.0 USER GUIDE
Superimpose
Superimpose chains/proteins over
other.
GEOMETRY TAB
Helps user to perform calculations on protein,
complexes for Dihedral angel, bond length,
centre of mass, centre of gravity.
Dihedral Angel
Tool to calculate angel between 4
atoms of protein target
OUTPUT
26 INVENTUS v1.0 USER GUIDE
To calculate, click on PLAY button
on top tab panel
A
n
g
Angle
Tool to calculate angle between 3
atoms of protein target
To calculate, click on PLAY button
on top tab panel
OUTPUT
PLAY
27 INVENTUS v1.0 USER GUIDE
Bond Length
Tool to calculate bond length
between 2 atoms of protein target
To calculate, click on PLAY button
on top tab panel.
28 INVENTUS v1.0 USER GUIDE
Centre of Mass
Tool to calculate centre of mass for
complete protein structure
Result is displayed at the bottom
c
o
l
u
m
n
.
Centre of Gravity
Tool to calculate centre of gravity for
complete protein structure
Result is displayed at the bottom
C
29 INVENTUS v1.0 USER GUIDE
Chapter 3
EnergyOptTM
- Module for optimizing
energy of protein target
(Modeled/Crystallized)
The protein structure optimizer minimizes the
energy of a protein target using combination of
steepest decent conjugate gradient minimization
algorithm using Cornell‟s force field equation.
Figure 13. EnergyOptTM
module
How to Run EnergyOptTM
Upload a pdb files in Inventus software
Click on EnergyOptTM
module
Select no of cycles to be run for steepest descent
and conjugate gradient (ex: 20 cycle each)
Select chain of protein file
Select type of minimization
Bonded Minimization
Non bonded minimization
30 INVENTUS v1.0 USER GUIDE
Complete Minimization
Click on RUN Button
Note: Higher the number of cycles in steepest
descent and conjugate gradient, better will be the
optimization.
Output View
Once program is finished, Status will be updated
as DONE. If program is still in running mode,
status will be shown as RUNNING along with
colored progress bar.
Once program is finished, under RESULT Tab
click VIEW
A pop up window will open displaying result of
minimization (Figure )
Figure 14. Energy Minimization result for 2ADF
31 INVENTUS v1.0 USER GUIDE
Chapter 4
MCSimulatorTM
- Module for Monte Carlo
Simulations
MCSimulator
TM is used to generate conformer using
three different methodologies
Perturbation of the terminal loop residue
Perturbation of any loop residue
Perturbation of any residue
Figure 15. MCSimulator
TM
How to Run MCSimulatorTM
Upload a pdb files in Inventus software
Click on MCSimulatorTM
module
Select chain of protein target on which Monte
Carlo simulations to be run
Select number of steps
Select type of methodology
Perturbation of the terminal loop residue
32 INVENTUS v1.0 USER GUIDE
Perturbation of any loop residue
Perturbation of any residue
Click on RUN Button
Note: Higher the number of cycles in steepest
descent and conjugate gradient, better will be the
optimization.
Output View
Once program is finished, Status will be updated
as DONE. If program is still in running mode,
status will be shown as RUNNING along with
colored progress bar.
Once program is finished, under RESULT Tab
click VIEW
A pop up window will open displaying result of
minimization (Figure )
Figure 16. Monte Carlo Simulations for 2ADF
33 INVENTUS v1.0 USER GUIDE
Chapter 5
PocketDetectorTM
- Module for discovering
active site in protein target
PocketDetector is a predictive tool of Inventus for
discovering active site in protein targets. Active sites are
given in ranking order and used as per user analysis
Figure 17. PocketDetector
TM
How to Run PocketDetector
TM
Upload a pdb files in Inventus software
Click on PocketDetectorTM
module
Select pdb file of protein target
Select chain of protein target where active site is
to be detected
Click on RUN Button
34 INVENTUS v1.0 USER GUIDE
Output View
Once program is finished, Status will be updated
as DONE. If program is still in running mode,
status will be shown as RUNNING along with
colored progress bar.
Figure 18. PocketDetector
How to view active site
Click on pdb ID of protein target on which you
calculated active site
Selected distance from ligand molecule for
which you would like to view active site (option:
2Å, 5Å & 10Å)
Click on any cavity and SAVE text file of active
site
USER can view text file by uploading saved pdb
file of active site
35 INVENTUS v1.0 USER GUIDE
Chapter 6
HitsGENTM
– Module for virtual high
throughput screening
HitsGen is a predictive tool of Inventus for undergoing
virtual high throughput screening.
Figure 19: HitsGen module on interface
Tabs in HitsGenTM
Molecules: Displays PDB‟s uploaded in
Inventus along with all the chains of each PDB
file selected.
Compound Libraries: Displays list of compound
libraries in Inventus
Generic – User can input customized
library of its own for running V-HTS on
selected protein active site
36 INVENTUS v1.0 USER GUIDE
Target Specific Class: Selection of
compound library as per class of protein
target
Kinases
GPCR‟s
Ion Channels
Nucleases
Proteases
Disease Specific: Inventus is loaded
with selective compounds which have
been discovered against multiple
diseases and can be used for initial hits
for running computational studies
Alzheimer‟s
Cytomegalovirus
Hepatitis
Parkinson‟s
Diabetes
Huntington
Influenza
Properties: User can select multiple properties
for running HitsGen module. Each of these
properties plays an important role while
screening compounds for selective protein
target.
Weiner Index
Hydrogen Bond Acceptor
Hydrogen Bond Donor
LogP
Molar Refractivity
Functional Group
- Acid
- Alochal
- Sulphate/Phosphate
- Amide
- Aldehyde/Ketone
- Ester
- Amine
- Ether
No. of aromatic rings
Formal Charge
Length of Molecule
Total. No. of Atoms
37 INVENTUS v1.0 USER GUIDE
Cut off Binding Energy
(Kcal/mol)
Figure 20. HitsGen run on 1AOE pdb file.
How to Run HitsGenTM
(In presence of
reference ligand)
Upload a pdb files in Inventus software
Click on HitsGen module from module tab
Select pdb file; Select Chain; Select ligand
Select type of library to be used from Compound
Libraries selection window
Select different physico-chemical properties
Click on RUN Button
Output View
Once program is finished, Status will be updated
as DONE. If program is still in running mode,
status will be shown as RUNNING along with
colored progress bar.
38 INVENTUS v1.0 USER GUIDE
Once program is finished, click on View link
under RESULT Tab for viewing result of High
Throughput Screening.
Figure 21. Result of HitsGen on pdb ID: 1AOE
On clicking View button, result will be
displayed in different window as Figure 4.
Details of compounds will shown along with
their physico-chemical parameters against
selective active site of protein target.
All compounds can also be exported on excel
sheet.
To view compound in Inventus, USER can copy
SMILE string and convert it into PDB/SDF file
using public software. PDB/SDF file of
compounds can be uploaded in Inventus.
How to Run HitsGenTM
(In absence of
reference ligand)
Upload a pdb files in Inventus software
Click on HitsGen module from module tab
Select pdb file; Select Chain; Select No ligand
39 INVENTUS v1.0 USER GUIDE
Upload binding pocket file in asked browser (If
binding pocket is not available, use
PocketDetectorTM
and calculate active site
Select type of library to be used from Compound
Libraries selection window
Select different physico-chemical properties
Click on RUN Button
Figure 22. HitsGen on protein ID: 1AiL without having reference ligand attached
Output View
Once program is finished, Status will be updated
as DONE. If program is still in running mode,
status will be shown as RUNNING along with
colored progress bar.
Once program is finished, click on View link
under RESULT Tab for viewing result of High
Throughput Screening.
40 INVENTUS v1.0 USER GUIDE
Chapter 7
BioAffTM
Module for calculating binding
energy of protein-ligand complex
HitsGen is a predictive tool of Inventus for calculating
out binding energy of protein-ligand complexes.
Figure 23. BioAff module for calculating Binding energy of complexes.
For calculating binding energy of protein-ligand
complex, two different methodologies are used. User can
selected any methodology of them for calculating
energy.
AM1 BCC
Gasteiger
How to Run BioAffTM
41 INVENTUS v1.0 USER GUIDE
Upload a pdb files in Inventus software from file
upload option
Click on BioAff module from module tab
Select pdb file; Select Chain and Select
Compound
Select type of methodology
Click on RUN Button
Figure 24. Running BioAff on protein ID: 1AOE using AM1 BCC methodology
Output View
Once program is finished, Status will be updated
as DONE. If program is still in running mode,
status will be shown as RUNNING along with
colored progress bar.
Once program is finished, click on View link
under RESULT Tab for viewing result of BioAff
module.
42 INVENTUS v1.0 USER GUIDE
Figure 25. Result of BioAff on 1AOE.
Once program is finished, Binding energy value
will be displayed under RESULT column and
status will show as DONE.
Result can also be exported to excel sheet by
clicking EXPORT button
43 INVENTUS v1.0 USER GUIDE
Chapter 8
NovoDockerTM
Module for Docking studies
HitsGen is a tool of Inventus for undergoing
docking studies. Selection of protein target file
and compound is necessary
Figure 26. NovoDockerTM
How to Run NovoDockerTM
Upload a pdb files in Inventus software
Click on NovoDockerTM
module
Select pdb file; Select Chain; Select NO ligand
Upload binding pocket site. If binding pocket
site is not available then calculate active site
using PocketDetectorTM
Upload Candidate ligand in Candidate Molecule
file name and path will be automatically selected
Click on RUN Button
44 INVENTUS v1.0 USER GUIDE
Output View
Once program is finished, Status will be updated
as DONE. If program is still in running mode,
status will be shown as RUNNING along with
colored progress bar.
Once program is finished, under RESULT Tab
CLICK and save Docking results on desktop .
Figure 27. Savings docking file on desktop
NovoDockerTM
will generate different
no. of docked poses and all be numbered
as per ascending order (eg: Rank 1 is
best docked pose).
Docked poses can be visualized in
Inventus under different mode of
visualizations for complex.
45 INVENTUS v1.0 USER GUIDE
Chapter 9
ClashOptTM
- Module for removing steric
clashes in protein structures
ClashOptTM
module is used to remove steric
clashes in protein structures based on phi and psi
angles. This tool helps in optimizing protein
structure for Drug Discovery research
Figure 28. ClashOpt
TM
How to Run NovoDockerTM
Upload a pdb files in Inventus software
Click on ClashOptTM
module
Select number of steps
Select chain of protein target on which Monte
Carlo simulations to be run
Click on RUN Button
46 INVENTUS v1.0 USER GUIDE
Output View
Once program is finished, Status will be updated
as DONE. If program is still in running mode,
status will be shown as RUNNING along with
colored progress bar.
Once program is finished, under RESULT Tab
click VIEW
A pop up window will open displaying result of
minimization (Figure )
Figure 29. ClashOpt for 2ADF Chain A.
47 INVENTUS v1.0 USER GUIDE
Chapter 10
PharmoPredictaTM
Module for calculating
ADME properties of molecules
PharmoPredicta
TM is a comprehensive predictive ADME
software system developed and validated to predict
relevant pharmacokinetic and ADME characteristics of
potential drugs. pk ExpressTM
is bought from US based
company G2 Research Inc. The system can be deployed
as a PC desktop application or as an ADME compute
engine in a larger cheminformatics system. Inventus
pkEXPRESS includes the following:
• Physiological Absorption Model
• Physiological Metabolism Model
• Physiological Distribution and Elimination Model
Figure 30. Opening wizard of Inventus pkExpress
TM
48 INVENTUS v1.0 USER GUIDE
How to Run PharmoPredictaTM
Click on PharmoPredictaTM
module
A new window of Inventus pkExpressTM
will
open in Inventus wizard
All operations for ADME will conducted on
Inventus pkExpressTM
wizard.
Note: A seprate manual designed by G2
Research Inc. for pkExpressTM
also included
with installation files.