Molecular insight into the sphingosine-1-phosphate pathway: from the unbinding from ApoM to receptor activation = Molekularer Einblick in den Reaktionsweg von Sphingosin-1-Phosphat
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| Main Author: | |
|---|---|
| Format: | Thesis Book |
| Language: | German |
| Published: |
Erlangen ; Nürnberg
2016
|
| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Physical Description: | XIX, 130 Seiten Illustrationen, Diagramme |
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MARC
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| 245 | 1 | 0 | |a Molecular insight into the sphingosine-1-phosphate pathway |b from the unbinding from ApoM to receptor activation = Molekularer Einblick in den Reaktionsweg von Sphingosin-1-Phosphat |c vorgelegt von Hansi Zhang aus Changchun |
| 246 | 1 | 1 | |a Molekularer Einblick in den Reaktionsweg von Sphingosin-1-Phosphat |
| 264 | 1 | |a Erlangen ; Nürnberg |c 2016 | |
| 300 | |a XIX, 130 Seiten |b Illustrationen, Diagramme | ||
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Record in the Search Index
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| adam_text |
MOLECULAR INSIGHT INTO THE
SPHINGOSINE-L-PHOSPHATE PATHWAY:
FROM THE UNBINDING FROM APOM
TO RECEPTOR ACTIVATION
MOLEKULARER EINBLICK IN DEN REAKTIONSWEG VON
SPHINGOSIN-L-PHOSPHAT:
VON DER ENTBINDUNG VON APOM
ZUR REZEPTORAKTIVIERUNG
DER NATURWISSENSCHAFTLICHEN FAKULTAET
DER FRIEDRICH-ALEXANDER-UNIVERSITAET ERLANGEN-NUERNBERG
ZUR
ERLANGUNG DES DOKTORGRADES DR. RER. NAT.
VORGELEGT VON
HANSI ZHANG
AUS CHANGCHUN
CONTENTS
DECLARATION OF AUTHORSHIP III
ACKNOWLEDGEMENTS V
ZUSAMMENFASSUNG VII
ABSTRACT IX
LIST OF ABBREVIATIONS XVII
1 INTRODUCTION 1
1.1 SPHINGOSINE-L-PHOSPHATE
.
2
1.1.1 SIP M ETABOLISM
. 3
1.1.2 SIP SECRETION AND
REGULATION. 5
1.1.3 INTRACELLULAR FUNCTIONS AND EXTRACELLULAR TRANSPORTS
. 6
1.2 THE SIP CARRIER A P O M
. 6
1.2.1 GENETIC INFORMATION AND DISTRIBUTION OF A P O M
.
8
1.2.2 STRUCTURE OF THE APOM P R O TE IN
. 9
1.2.3 APOM
REGULATION.
14
1.2.4 FUNCTION OF A P O M
.
15
1.3 THE SIP RECEPTOR
S1PR.
17
1.3.1 SUBTYPES AND GENETIC INFORMATION OF S1PR
.
17
1.3.2 STRUCTURE OF S 1P R
. 19
1.3.3 SIPR'S L IG A N D S
. 23
1.3.4 REGULATION AND FUNCTION OF SI PR
.
25
1.4 AIM OF THIS S TU D Y
.
27
2 THEORY AND METHODS 29
2.1 MOLECULAR DYNAMICS SIMULATIONS
.
30
2.1.1 THE BORN-OPPENHEIMER APPROXIMATION
.
31
2.1.2 FORCE F IE LD S
.
32
2.1.3 CLASSICAL D YNAM
ICS. 35
2.1.4 INTEGRATION
ALGORITHMS. 35
2.1.5 PERIODIC BOUNDARY CONDITIONS AND MINIMUM IMAGE CON
VENTION
.
36
2.1.6 TEMPERATURE AND PRESSURE C
OUPLING. 37
2.1.7 STEERED MOLECULAR DYNAMICS SIM ULATIONS
.
39
2.1.8 UMBRELLA SAMPLING M
ETHOD. 39
2.1.9 MARTINI COARSE-GRAINED M O D E L
.
41
2.2 TRAJECTORY ANALYSIS M
ETHODS. 43
2.2.1 PKA CALCULATION
.
43
2.2.2 FORCE DISTRIBUTION A N ALY
SIS. 45
2.2.3 POCKET VOLUME MEASUREMENTS
.
46
3 BINDING CHARACTERISTICS OF SPHINGOSINE-L-PHOSPHATE TO APOM HINTS
TO ASSISTED RELEASE MECHANISM VIA THE APOM CALYX-OPENING 49
3.1 MD SIMULATION O V E RV IE W
. 52
3.1.1 STARTING S TRU C TU RE
S. 52
3.1.2 FORCE FIELD PARAM
ETERS. 54
3.1.3 MD SIMULATION P ARAM
ETERS. 55
3.1.4 ENFORCED SIP UNBINDING AND UMBRELLA S AM PLING
.
55
3.2 PROTONATION OF SIP
.
57
3.3 CHARACTERISTICS OF SIP BINDING TO A P O M
.
59
3.4 APOM-SIP COMPLEX ASSOCIATED WITH LIPID L A Y E R
.
64
3.5 ENFORCED SIP U NBINDING
.
64
3.6 APOM MICROENVIRONMENT CHANGES DURING LIGAND UNBINDING . . 68
3.7 APOM CAVITY
VOLUME.
70
3.8 D
ISCUSSION.
72
4 SIP BINDING TO ITS RECEPTOR SIPI AND SIP-INDUCED RECEPTOR ACTI
VATION 75
4.1 SIMULATION SYSTEM O V E RV IE W
. 80
4.1.1 COARSE-GRAINED
SIMULATIONS. 80
4.1.2 ATOMISTIC S IM
ULATIONS. 82
4.1.3 FORCE DISTRIBUTION A N ALY SIS
.
84
4.2 SIP SPONTANEOUS BINDING TO THE SIPI RECEPTOR
.
84
4.3 BINDING MECHANISM OF SIP TO THE SIPI R ECEPTOR
.
85
4.4 SIP BINDING C
HARACTERISTICS.
87
4.5 SIPI RECEPTOR FLEXIBILITY
.
94
4.6 SIGNAL TRANSITION AND RECEPTOR ACTIVATION
.
95
4.7 LOOSE COUPLING OF CONNECTOR AND G PROTEIN BINDING S ITE
.
99
4.8 DISCUSSION & C
ONCLUSIONS.100
SUMMARY AND CONCLUSIONS 103
OUTLOOK 107
APPENDICES 109
A SIP MODEL AND PARAMETERS 109
BIBLIOGRAPHY H3 |
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| illustrated | Illustrated |
| indexdate | 2024-12-10T13:02:27Z |
| institution | BVB |
| language | German |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-029105561 |
| oclc_num | 954341494 |
| open_access_boolean | |
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| owner_facet | DE-29 DE-29T DE-355 DE-BY-UBR DE-12 |
| physical | XIX, 130 Seiten Illustrationen, Diagramme |
| publishDate | 2016 |
| publishDateSearch | 2016 |
| publishDateSort | 2016 |
| record_format | marc |
| spelling | Zhang, Hansi 1985- Verfasser (DE-588)1109080921 aut Molecular insight into the sphingosine-1-phosphate pathway from the unbinding from ApoM to receptor activation = Molekularer Einblick in den Reaktionsweg von Sphingosin-1-Phosphat vorgelegt von Hansi Zhang aus Changchun Molekularer Einblick in den Reaktionsweg von Sphingosin-1-Phosphat Erlangen ; Nürnberg 2016 XIX, 130 Seiten Illustrationen, Diagramme txt rdacontent n rdamedia nc rdacarrier Dissertation Friedrich-Alexander-Universität Erlangen-Nürnberg 2016 Metabolismus (DE-588)4169554-9 gnd rswk-swf Sphingosin (DE-588)4121703-2 gnd rswk-swf Sekundärer Bote (DE-588)4243447-6 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Sphingosin (DE-588)4121703-2 s Sekundärer Bote (DE-588)4243447-6 s Metabolismus (DE-588)4169554-9 s DE-604 DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029105561&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Zhang, Hansi 1985- Molecular insight into the sphingosine-1-phosphate pathway from the unbinding from ApoM to receptor activation = Molekularer Einblick in den Reaktionsweg von Sphingosin-1-Phosphat Metabolismus (DE-588)4169554-9 gnd Sphingosin (DE-588)4121703-2 gnd Sekundärer Bote (DE-588)4243447-6 gnd |
| subject_GND | (DE-588)4169554-9 (DE-588)4121703-2 (DE-588)4243447-6 (DE-588)4113937-9 |
| title | Molecular insight into the sphingosine-1-phosphate pathway from the unbinding from ApoM to receptor activation = Molekularer Einblick in den Reaktionsweg von Sphingosin-1-Phosphat |
| title_alt | Molekularer Einblick in den Reaktionsweg von Sphingosin-1-Phosphat |
| title_auth | Molecular insight into the sphingosine-1-phosphate pathway from the unbinding from ApoM to receptor activation = Molekularer Einblick in den Reaktionsweg von Sphingosin-1-Phosphat |
| title_exact_search | Molecular insight into the sphingosine-1-phosphate pathway from the unbinding from ApoM to receptor activation = Molekularer Einblick in den Reaktionsweg von Sphingosin-1-Phosphat |
| title_full | Molecular insight into the sphingosine-1-phosphate pathway from the unbinding from ApoM to receptor activation = Molekularer Einblick in den Reaktionsweg von Sphingosin-1-Phosphat vorgelegt von Hansi Zhang aus Changchun |
| title_fullStr | Molecular insight into the sphingosine-1-phosphate pathway from the unbinding from ApoM to receptor activation = Molekularer Einblick in den Reaktionsweg von Sphingosin-1-Phosphat vorgelegt von Hansi Zhang aus Changchun |
| title_full_unstemmed | Molecular insight into the sphingosine-1-phosphate pathway from the unbinding from ApoM to receptor activation = Molekularer Einblick in den Reaktionsweg von Sphingosin-1-Phosphat vorgelegt von Hansi Zhang aus Changchun |
| title_short | Molecular insight into the sphingosine-1-phosphate pathway |
| title_sort | molecular insight into the sphingosine 1 phosphate pathway from the unbinding from apom to receptor activation molekularer einblick in den reaktionsweg von sphingosin 1 phosphat |
| title_sub | from the unbinding from ApoM to receptor activation = Molekularer Einblick in den Reaktionsweg von Sphingosin-1-Phosphat |
| topic | Metabolismus (DE-588)4169554-9 gnd Sphingosin (DE-588)4121703-2 gnd Sekundärer Bote (DE-588)4243447-6 gnd |
| topic_facet | Metabolismus Sphingosin Sekundärer Bote Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029105561&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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