skip to main content
Guest
My Research
My Account
Sign out
Sign in
This feature requires javascript
Library Search
Find Databases
Browse Search
E-Journals A-Z
E-Books A-Z
Citation Linker
Help
Language:
English
Vietnamese
This feature required javascript
This feature requires javascript
Primo Advanced Search
All Library Resources
All
Course Materials
Course Materials
Primo Advanced Search Query Term
Show Results with:
criteria input
Any
in the title
as author/creator
in subject
Full Text
ISBN
ISSN
TOC
Keyword
Field
Show Results with:
in the title
Show Results with:
Any
in the title
as author/creator
in subject
Full Text
ISBN
ISSN
TOC
Keyword
Field
Show Results with:
criteria input
contains
is (exact)
starts with
Input search text:
Show Results with:
criteria input
AND
OR
NOT
Primo Advanced Search Query Term
Show Results with:
criteria input
Any
in the title
as author/creator
in subject
Full Text
ISBN
ISSN
TOC
Keyword
Field
Show Results with:
in the title
Show Results with:
Any
in the title
as author/creator
in subject
Full Text
ISBN
ISSN
TOC
Keyword
Field
Show Results with:
criteria input
contains
is (exact)
starts with
Input search text:
Show Results with:
criteria input
AND
OR
NOT
Primo Advanced Search Query Term
Show Results with:
criteria input
Any
in the title
as author/creator
in subject
Full Text
ISBN
ISSN
TOC
Keyword
Field
Show Results with:
in the title
Show Results with:
Any
in the title
as author/creator
in subject
Full Text
ISBN
ISSN
TOC
Keyword
Field
Show Results with:
criteria input
contains
is (exact)
starts with
Input search text:
Show Results with:
criteria input
AND
OR
NOT
Primo Advanced Search Query Term
Show Results with:
criteria input
Any
in the title
as author/creator
in subject
Full Text
ISBN
ISSN
TOC
Keyword
Field
Show Results with:
in the title
Show Results with:
Any
in the title
as author/creator
in subject
Full Text
ISBN
ISSN
TOC
Keyword
Field
Show Results with:
criteria input
contains
is (exact)
starts with
Input search text:
Show Results with:
criteria input
AND
OR
NOT
Primo Advanced Search Query Term
Show Results with:
criteria input
Any
in the title
as author/creator
in subject
Full Text
ISBN
ISSN
TOC
Keyword
Field
Show Results with:
in the title
Show Results with:
Any
in the title
as author/creator
in subject
Full Text
ISBN
ISSN
TOC
Keyword
Field
Show Results with:
criteria input
contains
is (exact)
starts with
Input search text:
Show Results with:
criteria input
AND
OR
NOT
Primo Advanced Search prefilters
Publication Date:
criteria input
Any year
Last year
Last 2 years
Last 5 years
Last 10 years
Last 20 years
Start Year:
criteria input
Day
01
02
03
04
05
06
07
08
09
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
criteria input
Month
01
02
03
04
05
06
07
08
09
10
11
12
query input
End Year:
criteria input
Day
01
02
03
04
05
06
07
08
09
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
criteria input
Month
01
02
03
04
05
06
07
08
09
10
11
12
query input
Material Type:
criteria input
All items
Books
Articles
Journals
Audio Visual
Maps
Graduate theses
Syllabus
Lectures
Undergraduate theses
Language:
criteria input
Any language
Vietnamese
English
French
German
Chinese
Search Scope:
All Library Resources
Print Resources
Digital Resources
Online E-Resources
Simple Search
This feature requires javascript
Computational Tool to Design Small Synthetic Inhibitors Selective for XIAP-BIR3 Domain
Molecules (Basel, Switzerland), 2023-07, Vol.28 (13)
[Peer Reviewed Journal]
Attribution ;ISSN: 1420-3049 ;EISSN: 1420-3049 ;DOI: 10.3390/molecules28135155
Full text available
Citations
Cited by
View Online
Details
Recommendations
Reviews
Times Cited
External Links
This feature requires javascript
Actions
Add to My Research
Remove from My Research
E-mail
Print
Permalink
Citation
EasyBib
EndNote
RefWorks
Delicious
Export RIS
Export BibTeX
This feature requires javascript
Title:
Computational Tool to Design Small Synthetic Inhibitors Selective for XIAP-BIR3 Domain
Author:
Farag, Marc
;
Kieffer, Charline
;
Guedeney, Nicolas
;
Voisin-Chiret, Anne Sophie
;
Sopkova-de Oliveira Santos, Jana
Subjects:
Computer Science
Is Part Of:
Molecules (Basel, Switzerland), 2023-07, Vol.28 (13)
Description:
X-linked inhibitor of apoptosis protein (XIAP) exercises its biological function by locking up and inhibiting essential caspase-3, -7 and -9 toward apoptosis execution. It is overexpressed in multiple human cancers, and it plays an important role in cancer cells’ death skipping. Inhibition of XIAP-BIR3 domain and caspase-9 interaction was raised as a promising strategy to restore apoptosis in malignancy treatment. However, XIAP-BIR3 antagonists also inhibit cIAP1-2 BIR3 domains, leading to serious side effects. In this study, we worked on a theoretical model that allowed us to design and optimize selective synthetic XIAP-BIR3 antagonists. Firstly, we assessed various MM-PBSA strategies to predict the XIAP-BIR3 binding affinities of synthetic ligands. Molecular dynamics simulations using hydrogen mass repartition as an additional parametrization with and without entropic term computed by the interaction entropy approach produced the best correlations. These simulations were then exploited to generate 3D pharmacophores. Following an optimization with a training dataset, five features were enough to model XIAP-BIR3 synthetic ligands binding to two hydrogen bond donors, one hydrogen bond acceptor and two hydrophobic groups. The correlation between pharmacophoric features and computed MM-PBSA free energy revealed nine residues as crucial for synthetic ligand binding: Thr308, Glu314, Trp323, Leu307, Asp309, Trp310, Gly306, Gln319 and Lys297. Ultimately, and three of them seemed interesting to use to improve XIAP-BR3 versus cIAP-BIR3 selectivity: Lys297, Thr308 and Asp309.
Publisher:
MDPI
Language:
English
Identifier:
ISSN: 1420-3049
EISSN: 1420-3049
DOI: 10.3390/molecules28135155
Source:
Geneva Foundation Free Medical Journals at publisher websites
Hyper Article en Ligne (HAL) (Open Access)
PubMed Central
Alma/SFX Local Collection
ProQuest Central
DOAJ Directory of Open Access Journals
This feature requires javascript
This feature requires javascript
Back to results list
Previous
Result
17
Next
This feature requires javascript
This feature requires javascript
Searching Remote Databases, Please Wait
Searching for
in
scope:(TDTS),scope:(SFX),scope:(TDT),scope:(SEN),primo_central_multiple_fe
Show me what you have so far
This feature requires javascript
This feature requires javascript