Computational methods for assessing drug-target residence times in bacterial enoyl-ACP reductases and predicting small-molecule permeability for the Mycobacterium tuberculosis cell wall: = Computermethoden zur Bestimmung von Protein-Ligand Verweilzeiten in bakteriellen Enoyl-ACP Reduktasen und Vorhersage der Permeabilitätswahrscheinlichkeit kleiner Moleküle gegenüber der Mycobacterium tuberculosis Zellwand
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
Würzburg
Oktober 2015
|
| Schlagworte: | |
| Online-Zugang: | Volltext Inhaltsverzeichnis |
| Beschreibung: | XV, 227 Seiten Illustrationen, Diagramme |
Internformat
MARC
| LEADER | 00000nam a2200000 c 4500 | ||
|---|---|---|---|
| 001 | BV044203608 | ||
| 003 | DE-604 | ||
| 005 | 20170515 | ||
| 007 | t | ||
| 008 | 170301s2015 a||| m||| 00||| eng d | ||
| 035 | |a (OCoLC)976035158 | ||
| 035 | |a (DE-599)BVBBV044203608 | ||
| 040 | |a DE-604 |b ger |e rda | ||
| 041 | 0 | |a eng | |
| 049 | |a DE-384 |a DE-473 |a DE-703 |a DE-1051 |a DE-824 |a DE-29 |a DE-12 |a DE-91 |a DE-19 |a DE-1049 |a DE-92 |a DE-739 |a DE-898 |a DE-355 |a DE-706 |a DE-20 |a DE-1102 |a DE-860 |a DE-2174 | ||
| 084 | |a VC 5070 |0 (DE-625)147074: |2 rvk | ||
| 100 | 1 | |a Merget, Benjamin |d ca. 21. Jh. |e Verfasser |0 (DE-588)1126582158 |4 aut | |
| 245 | 1 | 0 | |a Computational methods for assessing drug-target residence times in bacterial enoyl-ACP reductases and predicting small-molecule permeability for the Mycobacterium tuberculosis cell wall |b = Computermethoden zur Bestimmung von Protein-Ligand Verweilzeiten in bakteriellen Enoyl-ACP Reduktasen und Vorhersage der Permeabilitätswahrscheinlichkeit kleiner Moleküle gegenüber der Mycobacterium tuberculosis Zellwand |c vorgelegt von Benjamin Merget aus Aschaffenburg |
| 246 | 1 | 1 | |a Computermethoden zur Bestimmung von Protein-Ligand Verweilzeiten in bakteriellen Enoyl-ACP Reduktasen und Vorhersage der Permeabilitätswahrscheinlichkeit kleiner Moleküle gegenüber der Mycobacterium tuberculosis Zellwand |
| 264 | 1 | |a Würzburg |c Oktober 2015 | |
| 300 | |a XV, 227 Seiten |b Illustrationen, Diagramme | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |b Dissertation |c Julius-Maximilians-Universität Würzburg |d 2016 | ||
| 546 | |a Zusammenfassung in deutscher und englischer Sprache | ||
| 650 | 0 | 7 | |a Permeabilität |0 (DE-588)4173828-7 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Arzneimitteldesign |0 (DE-588)4278218-1 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Molekulardynamik |0 (DE-588)4170370-4 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Computational chemistry |0 (DE-588)4290091-8 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Enoyl-acyl-carrier-protein-Reductase |g Enoyl-[acyl-carrier-protein]-Reductase |0 (DE-588)4481400-8 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Tuberkelbakterium |0 (DE-588)4186384-7 |2 gnd |9 rswk-swf |
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 689 | 0 | 0 | |a Computational chemistry |0 (DE-588)4290091-8 |D s |
| 689 | 0 | 1 | |a Arzneimitteldesign |0 (DE-588)4278218-1 |D s |
| 689 | 0 | 2 | |a Molekulardynamik |0 (DE-588)4170370-4 |D s |
| 689 | 0 | 3 | |a Permeabilität |0 (DE-588)4173828-7 |D s |
| 689 | 0 | 4 | |a Tuberkelbakterium |0 (DE-588)4186384-7 |D s |
| 689 | 0 | 5 | |a Enoyl-acyl-carrier-protein-Reductase |g Enoyl-[acyl-carrier-protein]-Reductase |0 (DE-588)4481400-8 |D s |
| 689 | 0 | |5 DE-604 | |
| 776 | 1 | 8 | |i Erscheint auch als |n Online-Ausgabe, PDF |o urn:nbn:de:bvb:20-opus-127386 |
| 856 | 4 | 1 | |u https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-127386 |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 2 | |m DNB Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029610069&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 912 | |a ebook | ||
| 999 | |a oai:aleph.bib-bvb.de:BVB01-029610069 | ||
Datensatz im Suchindex
| _version_ | 1804177339921203200 |
|---|---|
| adam_text | C OM PUTATIONAL M ETHODS FOR ASSESSING
DRUG-TARGET RESIDENCE TIM ES IN BACTERIAL
ENOYL-A C P REDUCTASES AND PREDICTING
SM ALL-M OLECULE PERM EABILITY FOR TH E
M YCO B A CTERIU M TUBERCULOSIS CELL WALL
DISSERTATION ZUR ERLANGUNG DES
NATURWISSENSCHAFTLICHEN DOKTORGRADES DER
JULIUS-MAXIMILIANS-UNIVERSITAET WUERZBURG
VORGELEGT VON
BENJAMIN MER GET
AUS ASCHAFFENBURG
WUERZBURG, OKTOBER 2015
CONTENTS
C ON TEN TS XI
1 IN TRO D U CTIO N 1
1.1 EARLY ANTIBIOTIC RESEARCH AND RESISTAN CES
.......................................................
1
1.2 MYCOBACTERIUM
TUBERCULOSIS.............................................................................
2
1.3 METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS
....................................................
3
1.4 SCOPE OF THIS WORK*RATIONAL RESIDENCE TIME MODULATION AND
PERMEABILITY
PREDICTION TO SUPPORT ANTIBACTERIAL DRUG D E S IG N
...........................................
3
1 R EV EA LIN G TH E M OLECU LAR D E TER M IN A N TS O F D RU G -T A RG
ET R ESID EN CE
T IM ES O F B A CTERIA L E N O Y L-A C P R E D U C TA SES U SIN G M O
LECU LA R D Y N A M
ICS S IM U LATION S 7
2 B ACKGROUND 9
2.1 FAS II AND ENOYL-ACP
REDUCTASES....................................................................
9
2.1.1 FATTY ACID SYNTHESIS TYPE I I
................................................................. 9
2.1.2 THE ENOYL-ACP REDUCTASES OF M. TUBERCULOSIS AND 5. AUREUS .... 10
2.1.3 INHIBITION OF MYCOBACTERIUM TUBERCULOSIS INHA BY DIPHENYLETHERS .
11
2.1.4 INHIBITION OF STAPHYLOCOCCUS AUREUS FABI BY DIPHENYLETHERS .... 13
2.2 BINDING AFFINITY AND DRUG-TARGET RESIDENCE T I M E
............................................... 14
2.3 COMPUTATIONAL METHODS FOR STRUCTURAL, ENERGETIC AND KINETIC
CHARACTERI
ZATION OF PROTEIN-LIGAND C O M P LE X E S
....................................................................
14
2.3.1 PRINCIPLES OF MOLECULAR DYNAMICS SIM U LA TIO N
S..................................17
2.3.1.1 MOLECULAR MECHANICAL FORCE
FIELDS............................................17
2.3.1.2 PARAMETERIZATION OF PROTEIN-LIGAND S Y S TE M S
.........................
19
2.3.1.3 EQUATIONS OF MOTION AND THEIR INTEGRATION
............................
20
2.3.1.4 ENHANCED SAMPLING TECH N IQ U
ES...............................................22
2.3.1.5 STEERED MOLECULAR D Y N A M IC S
..................
23
2.3.2 EVALUATION OF MD DATA
..........................................................................
25
2.3.3 EVALUATION OF SMD D A T A
..........................................................................
26
2.3.3.1 RECONSTRUCTION OF WORK
PROFILES...............................................26
2.3.3.2 RECONSTRUCTION OF PMF PROFILES USING JARZYNSKI*S EQUALITY 26
2.4 ANALYSIS TO O LS
.........................................................................................................27
3 S LOW -ON SET IN H IB ITION O F
M YCOBACTERIUM TUBERCULOSIS
INHA : R EVEALIN G
M OLECULAR D ETERM IN AN TS O F RESID EN CE TIM E BY M D SIM U LATION S
29
3.1
INTRODUCTION............................................................................................................29
3.2 BINDING POCKET DYNAMICS AND CONFORMATIONAL FAMILIES
..................................
31
3.3 SBL DYNAMICS AND SECONDARY STRUCTURE
ANALYSIS...............................................38
3.4 HYDROGEN BOND INTERACTIONS AND BINDING MODE ANALYSIS
..................................
39
3.5 INFLUENCE OF ORT/ZO-SUBSTITUTED B -RIN G
.................................................................
43
3.6 COMPARISON WITH EXPERIMENTAL S TR U C TU R E S
........................................................ 46
3.7 DETERMINANTS OF RESIDENCE TIME AND IMPLICATIONS FOR DRUG DESIGN
.................
49
3.8 CONCLUSION
............................................................................................................
51
3.9 M ETH O D
S..................................................................................................................
52
3.9.1 PROTEIN AND LIGAND P RE P A RA TIO N
..............................................................
52
3.9.2 MOLECULAR DYNAMICS SIM U LA TIO N S
...........................................................
53
4 M D SIM U LATION S O F 2 *,5 *-D ISU B STITU TED D IP H EN Y LETH ERS
IN INHA 55
4.1 SYSTEM
PREPARATION................................................................................................
55
4.2 R
ESULTS......................................................................................................................56
4.2.1 THE ILE202-VAL203-METL03
SUBPOCKET..................................................... 56
4.2.2 BACKBONE AND SBL STAB ILITY
....................................................................
60
4.2.3 BINDING POCKET STABILITY AND CONFORMATIONAL FAMILY ASSIGNMENT . .
61
4.2.4 LIGAND STAB ILITY
..........................................................................................64
4.2.5 ANALYSIS OF M E TL6 1
....................................................................................67
4.3 D
ISCUSSION...............................................................................................................
68
4.4 CONCLUSION
............................................................................................................
74
5 A N ACCU RATE AND Q U A N TITA TIV E P RED ICTION M OD EL FOR D RU
G-TARGET RESI
D EN CE TIM E O F
STAPHYLOCOCCUS AUREUS
FABI IN H IB ITORS BASED ON S TEERED
M OLECU LAR D Y N A M ICS 75
5.1 PROTEIN AND LIGAND P RE P A RA TIO N
...........................................................................75
5.2 DETERMINING THE LIGAND EGRESS ROUTE
.................................................................
77
5.3 STEERED MOLECULAR DYNAMICS SIM ULATIONS
...........................................................
78
5.4 STRUCTURAL DYNAMICS OF THE FABI BINDING P O C K E
T...............................................78
5.5 FREE ENERGY
PROFILES................................................................................................81
5.6 LINEAR MODELS OF RESIDENCE T IM E
..........................................................................
85
5.7 FLUCTUATIONS OF WORK V A LU E S
................................................................................
88
5.8 CORRELATION TO EXPERIMENTAL K I
..........................................................................
89
5.9 PARAMETER SELECTION AND OPTIM IZATION
.................................................................
93
5.10 CONCLUSION
............................................................................................................
94
6 T H E E L AND E L* STA TE S O F IN HA IN H IB ITION REV ISITED 95
6.1 COMPARISON OF EXPERIMENTAL INHA CRYSTAL S TR U C TU R E S
......................................96
6.2 MD SIM
ULATIONS....................................................................................................
100
6.2.1 SYSTEM
PREPARATION..................................................................................100
6.2.2 BACKBONE S TA B ILITY
..................................................................................102
6.2.3 BINDING POCKET CONFORMATIONS
...............................................................
102
6.2.4 HYDROGEN BOND A N A LY S IS
.........................................................................103
6.2.5 SBL S TA B ILITY
...........................................................................................
103
6.2.6 ANALYSIS OF CRYSTAL PACKING E FFE C T
.........................................................
105
6.2.7 C O N C LU SIO N
..............................................................................................
107
6.3 STEERED MD SIM U LA TIO N
S.....................................................................................108
6.3.1 SYSTEM
PREPARATION..................................................................................109
6.3.2 SMD
RESULTS..............................................................................................
109
6.4 CONCLUSION
..........................................................................................................
113
7 SUM M ARY * P ART I 115
II P R E D IC TIO N O F
M YCOBACTERIUM TUBERCULOSIS
C ELL W ALL P ERM EA B IL
ITY: D EV ELO P M EN T O F M Y CP ERM C H ECK AN D ITS A P P LICA TIO N
IN V IRTU A L
S CREEN IN G FOR A N TIM Y CO B A CTERIA L S U B STA N CES 117
8 B ACKGROUND 119
8.1 THE MYCOBACTERIUM TUBERCULOSIS CELL WALL HAMPERS ANTITUBERCULAR DRUG
D E S IG N
...................................................................................................................
119
8.2 MOLECULAR
DESCRIPTORS...........................................................................................
120
8.2.1 MOLECULAR DESCRIPTORS IN DRUG D E S IG N
................................................... 120
8.2.2 DESCRIPTOR CALCULATION S O FTW A RE
............................................................
121
8.3 STATISTICAL METHODS .
.
..........................................................................................
122
8.3.1 PRINCIPAL COMPONENT A N A LY S IS
...............................................................
122
8.3.2 LOGISTIC RE G RE SSIO N
..................................................................................123
8.3.3 RECEIVER OPERATING CH ARAC TE RISTIC
.........................................................
124
8.4 ANALYSIS TO O LS
.......................................................................................................
125
9 M YCP ERM C HECK: TH E
M YCOBACTERIUM TUBERCULOSIS
P ERM EAB ILITY PREDIC
TION TO O L FOR SM ALL M OLECULES 127
9.1 D A TA SE
TS................................................................................................................
127
9.2 DESCRIPTOR SELECTION AND VISUALIZATION
...............................................................
128
9.3 PCA AND LOGISTIC REGRESSION M E T H O D
...............................................................
132
9.4
EVALUATION.............................................................................................................
134
9.5 IM PLEM
ENTATION....................................................................................................
141
9.5.1 STAND-ALONE VERSION
...............................................................................143
9.6 PAD E L -D
ESCRIPTOR..............................................................................................
143
9.6.1 DESCRIPTOR SELECTION
...............................................................................143
9.6.2 PCA AND LOGISTIC REGRESSION M E T H O D
...................................................
144
9.6.3 EVALUATION
..............................................................................................
145
9.6.4 IM PLEM
ENTATION........................................................................................146
9.7
DISCUSSION.............................................................................................................
146
10 P ERM EAB ILITY P RED ICTION , D OCKING AND M D SIM U LATION S LEAD
TO SU GGES
TION O F P O TEN TIA L IN HA IN H IB ITORS 151
10.1 EXPLORATION OF THE M. TUBERCULOSIS PERMEABILITY SPACE
.
..............................
151
10.1.1 PERMEABILITY PREDICTION FOR THE ZINC D A TA B A S E
.................................151
10.1.2 DISTRIBUTIONS OF DESCRIPTOR AND ADMET D A T A
....................................152
10.1.3 CORRELATIONS IN DESCRIPTOR D A T A
............................................................
152
10.1.4 FILTERING OF ZINC FOR DESIRABLE PHYSICO-CHEMICAL AND ADMET
PROPERTIES AND SUBSEQUENT D O C K IN G
......................................................
158
10.2 DOCKING AND MD SIMULATIONS SUGGEST POTENTIAL INHA IN H IB ITO RS
...............
161
10.2.1 DOCKING OF ZINC03526947 D E RIV A TIV E S
................................................ 161
10.2.2 MD
SIMULATIONS........................................................................................164
10.2.2.1 RMSD AND DISTANCES
............................................................ 165
10.2.2.2 2D-RMSD ANALYSIS
..................................................................
167
10.2.2.3 CLUSTERING ANALYSIS
..................................................................
168
10.2.2.4 SUMMARY OF MD RESULTS OF DERIVATIVES M OD5 TO M O D L L . 169
10.2.3 AN ADDITIONAL ZINC03526947 DERIVATIVE: MOD 12 172
10.2.4 STEERED MD SIM ULATIO N
S.........................................................................172
10.3 EVALUATION OF SIMILAR C O M P O U N D S
.....................................................................
175
10.3.1 ACTIVITY D A T A
...........................................................................................
175
10.3.2 MD AND SMD SIM
ULATIONS......................................................................175
10.4 CONCLUSION
..........................................................................................................
177
11 SUM M ARY - P A RT II 179
S UM M ARY 181
MOLECULAR DETERMINANTS OF DRUG-TARGET RESIDENCE TIMES OF BACTERIAL
ENOYL-
ACP R E D U C TA SE S
.................................................................................................
181
PREDICTION OF MYCOBACTERIUM TUBERCULOSIS CELL WALL P E RM E A B ILITY
.......................
182
Z U SAM M ENFASSUNG 183
MOLEKULARE DETERMINANTEN VON WIRKSTOFF-ANGRIFFSZIEL VERWEILZEITEN
BAKTERIELLER
ENOYL-ACP R E D U K TA S E N
.....................................................................................183
VORHERSAGE VON MYCOBACTERIUM TUBERCULOSIS ZELLWAND PERM EABILITAET
......................
184
B IB LIOGRAP H Y 187
L IST O F F IGURES 209
L IST O F T ABLES 213
A B B REV IA TIO N S 215
A SM D SIM U LATION P RO TO CO L SU M M ARY 217
B S TAN D -ALON E VERSION O F M YCP ERM C H ECK 219
|
| any_adam_object | 1 |
| author | Merget, Benjamin ca. 21. Jh |
| author_GND | (DE-588)1126582158 |
| author_facet | Merget, Benjamin ca. 21. Jh |
| author_role | aut |
| author_sort | Merget, Benjamin ca. 21. Jh |
| author_variant | b m bm |
| building | Verbundindex |
| bvnumber | BV044203608 |
| classification_rvk | VC 5070 |
| collection | ebook |
| ctrlnum | (OCoLC)976035158 (DE-599)BVBBV044203608 |
| discipline | Chemie / Pharmazie |
| format | Thesis Book |
| fullrecord | <?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>03111nam a2200505 c 4500</leader><controlfield tag="001">BV044203608</controlfield><controlfield tag="003">DE-604</controlfield><controlfield tag="005">20170515 </controlfield><controlfield tag="007">t</controlfield><controlfield tag="008">170301s2015 a||| m||| 00||| eng d</controlfield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)976035158</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)BVBBV044203608</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-604</subfield><subfield code="b">ger</subfield><subfield code="e">rda</subfield></datafield><datafield tag="041" ind1="0" ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="049" ind1=" " ind2=" "><subfield code="a">DE-384</subfield><subfield code="a">DE-473</subfield><subfield code="a">DE-703</subfield><subfield code="a">DE-1051</subfield><subfield code="a">DE-824</subfield><subfield code="a">DE-29</subfield><subfield code="a">DE-12</subfield><subfield code="a">DE-91</subfield><subfield code="a">DE-19</subfield><subfield code="a">DE-1049</subfield><subfield code="a">DE-92</subfield><subfield code="a">DE-739</subfield><subfield code="a">DE-898</subfield><subfield code="a">DE-355</subfield><subfield code="a">DE-706</subfield><subfield code="a">DE-20</subfield><subfield code="a">DE-1102</subfield><subfield code="a">DE-860</subfield><subfield code="a">DE-2174</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">VC 5070</subfield><subfield code="0">(DE-625)147074:</subfield><subfield code="2">rvk</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Merget, Benjamin</subfield><subfield code="d">ca. 21. Jh.</subfield><subfield code="e">Verfasser</subfield><subfield code="0">(DE-588)1126582158</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Computational methods for assessing drug-target residence times in bacterial enoyl-ACP reductases and predicting small-molecule permeability for the Mycobacterium tuberculosis cell wall</subfield><subfield code="b">= Computermethoden zur Bestimmung von Protein-Ligand Verweilzeiten in bakteriellen Enoyl-ACP Reduktasen und Vorhersage der Permeabilitätswahrscheinlichkeit kleiner Moleküle gegenüber der Mycobacterium tuberculosis Zellwand</subfield><subfield code="c">vorgelegt von Benjamin Merget aus Aschaffenburg</subfield></datafield><datafield tag="246" ind1="1" ind2="1"><subfield code="a">Computermethoden zur Bestimmung von Protein-Ligand Verweilzeiten in bakteriellen Enoyl-ACP Reduktasen und Vorhersage der Permeabilitätswahrscheinlichkeit kleiner Moleküle gegenüber der Mycobacterium tuberculosis Zellwand</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="a">Würzburg</subfield><subfield code="c">Oktober 2015</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">XV, 227 Seiten</subfield><subfield code="b">Illustrationen, Diagramme</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="502" ind1=" " ind2=" "><subfield code="b">Dissertation</subfield><subfield code="c">Julius-Maximilians-Universität Würzburg</subfield><subfield code="d">2016</subfield></datafield><datafield tag="546" ind1=" " ind2=" "><subfield code="a">Zusammenfassung in deutscher und englischer Sprache</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Permeabilität</subfield><subfield code="0">(DE-588)4173828-7</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Arzneimitteldesign</subfield><subfield code="0">(DE-588)4278218-1</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Molekulardynamik</subfield><subfield code="0">(DE-588)4170370-4</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Computational chemistry</subfield><subfield code="0">(DE-588)4290091-8</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Enoyl-acyl-carrier-protein-Reductase</subfield><subfield code="g">Enoyl-[acyl-carrier-protein]-Reductase</subfield><subfield code="0">(DE-588)4481400-8</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Tuberkelbakterium</subfield><subfield code="0">(DE-588)4186384-7</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="655" ind1=" " ind2="7"><subfield code="0">(DE-588)4113937-9</subfield><subfield code="a">Hochschulschrift</subfield><subfield code="2">gnd-content</subfield></datafield><datafield tag="689" ind1="0" ind2="0"><subfield code="a">Computational chemistry</subfield><subfield code="0">(DE-588)4290091-8</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2="1"><subfield code="a">Arzneimitteldesign</subfield><subfield code="0">(DE-588)4278218-1</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2="2"><subfield code="a">Molekulardynamik</subfield><subfield code="0">(DE-588)4170370-4</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2="3"><subfield code="a">Permeabilität</subfield><subfield code="0">(DE-588)4173828-7</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2="4"><subfield code="a">Tuberkelbakterium</subfield><subfield code="0">(DE-588)4186384-7</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2="5"><subfield code="a">Enoyl-acyl-carrier-protein-Reductase</subfield><subfield code="g">Enoyl-[acyl-carrier-protein]-Reductase</subfield><subfield code="0">(DE-588)4481400-8</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2=" "><subfield code="5">DE-604</subfield></datafield><datafield tag="776" ind1="1" ind2="8"><subfield code="i">Erscheint auch als</subfield><subfield code="n">Online-Ausgabe, PDF</subfield><subfield code="o">urn:nbn:de:bvb:20-opus-127386</subfield></datafield><datafield tag="856" ind1="4" ind2="1"><subfield code="u">https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-127386</subfield><subfield code="x">Resolving-System</subfield><subfield code="z">kostenfrei</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="m">DNB Datenaustausch</subfield><subfield code="q">application/pdf</subfield><subfield code="u">http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029610069&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA</subfield><subfield code="3">Inhaltsverzeichnis</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">ebook</subfield></datafield><datafield tag="999" ind1=" " ind2=" "><subfield code="a">oai:aleph.bib-bvb.de:BVB01-029610069</subfield></datafield></record></collection> |
| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
| genre_facet | Hochschulschrift |
| id | DE-604.BV044203608 |
| illustrated | Illustrated |
| indexdate | 2024-07-10T07:46:31Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-029610069 |
| oclc_num | 976035158 |
| open_access_boolean | 1 |
| owner | DE-384 DE-473 DE-BY-UBG DE-703 DE-1051 DE-824 DE-29 DE-12 DE-91 DE-BY-TUM DE-19 DE-BY-UBM DE-1049 DE-92 DE-739 DE-898 DE-BY-UBR DE-355 DE-BY-UBR DE-706 DE-20 DE-1102 DE-860 DE-2174 |
| owner_facet | DE-384 DE-473 DE-BY-UBG DE-703 DE-1051 DE-824 DE-29 DE-12 DE-91 DE-BY-TUM DE-19 DE-BY-UBM DE-1049 DE-92 DE-739 DE-898 DE-BY-UBR DE-355 DE-BY-UBR DE-706 DE-20 DE-1102 DE-860 DE-2174 |
| physical | XV, 227 Seiten Illustrationen, Diagramme |
| psigel | ebook |
| publishDate | 2015 |
| publishDateSearch | 2015 |
| publishDateSort | 2015 |
| record_format | marc |
| spelling | Merget, Benjamin ca. 21. Jh. Verfasser (DE-588)1126582158 aut Computational methods for assessing drug-target residence times in bacterial enoyl-ACP reductases and predicting small-molecule permeability for the Mycobacterium tuberculosis cell wall = Computermethoden zur Bestimmung von Protein-Ligand Verweilzeiten in bakteriellen Enoyl-ACP Reduktasen und Vorhersage der Permeabilitätswahrscheinlichkeit kleiner Moleküle gegenüber der Mycobacterium tuberculosis Zellwand vorgelegt von Benjamin Merget aus Aschaffenburg Computermethoden zur Bestimmung von Protein-Ligand Verweilzeiten in bakteriellen Enoyl-ACP Reduktasen und Vorhersage der Permeabilitätswahrscheinlichkeit kleiner Moleküle gegenüber der Mycobacterium tuberculosis Zellwand Würzburg Oktober 2015 XV, 227 Seiten Illustrationen, Diagramme txt rdacontent n rdamedia nc rdacarrier Dissertation Julius-Maximilians-Universität Würzburg 2016 Zusammenfassung in deutscher und englischer Sprache Permeabilität (DE-588)4173828-7 gnd rswk-swf Arzneimitteldesign (DE-588)4278218-1 gnd rswk-swf Molekulardynamik (DE-588)4170370-4 gnd rswk-swf Computational chemistry (DE-588)4290091-8 gnd rswk-swf Enoyl-acyl-carrier-protein-Reductase Enoyl-[acyl-carrier-protein]-Reductase (DE-588)4481400-8 gnd rswk-swf Tuberkelbakterium (DE-588)4186384-7 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Computational chemistry (DE-588)4290091-8 s Arzneimitteldesign (DE-588)4278218-1 s Molekulardynamik (DE-588)4170370-4 s Permeabilität (DE-588)4173828-7 s Tuberkelbakterium (DE-588)4186384-7 s Enoyl-acyl-carrier-protein-Reductase Enoyl-[acyl-carrier-protein]-Reductase (DE-588)4481400-8 s DE-604 Erscheint auch als Online-Ausgabe, PDF urn:nbn:de:bvb:20-opus-127386 https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-127386 Resolving-System kostenfrei Volltext DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029610069&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Merget, Benjamin ca. 21. Jh Computational methods for assessing drug-target residence times in bacterial enoyl-ACP reductases and predicting small-molecule permeability for the Mycobacterium tuberculosis cell wall = Computermethoden zur Bestimmung von Protein-Ligand Verweilzeiten in bakteriellen Enoyl-ACP Reduktasen und Vorhersage der Permeabilitätswahrscheinlichkeit kleiner Moleküle gegenüber der Mycobacterium tuberculosis Zellwand Permeabilität (DE-588)4173828-7 gnd Arzneimitteldesign (DE-588)4278218-1 gnd Molekulardynamik (DE-588)4170370-4 gnd Computational chemistry (DE-588)4290091-8 gnd Enoyl-acyl-carrier-protein-Reductase Enoyl-[acyl-carrier-protein]-Reductase (DE-588)4481400-8 gnd Tuberkelbakterium (DE-588)4186384-7 gnd |
| subject_GND | (DE-588)4173828-7 (DE-588)4278218-1 (DE-588)4170370-4 (DE-588)4290091-8 (DE-588)4481400-8 (DE-588)4186384-7 (DE-588)4113937-9 |
| title | Computational methods for assessing drug-target residence times in bacterial enoyl-ACP reductases and predicting small-molecule permeability for the Mycobacterium tuberculosis cell wall = Computermethoden zur Bestimmung von Protein-Ligand Verweilzeiten in bakteriellen Enoyl-ACP Reduktasen und Vorhersage der Permeabilitätswahrscheinlichkeit kleiner Moleküle gegenüber der Mycobacterium tuberculosis Zellwand |
| title_alt | Computermethoden zur Bestimmung von Protein-Ligand Verweilzeiten in bakteriellen Enoyl-ACP Reduktasen und Vorhersage der Permeabilitätswahrscheinlichkeit kleiner Moleküle gegenüber der Mycobacterium tuberculosis Zellwand |
| title_auth | Computational methods for assessing drug-target residence times in bacterial enoyl-ACP reductases and predicting small-molecule permeability for the Mycobacterium tuberculosis cell wall = Computermethoden zur Bestimmung von Protein-Ligand Verweilzeiten in bakteriellen Enoyl-ACP Reduktasen und Vorhersage der Permeabilitätswahrscheinlichkeit kleiner Moleküle gegenüber der Mycobacterium tuberculosis Zellwand |
| title_exact_search | Computational methods for assessing drug-target residence times in bacterial enoyl-ACP reductases and predicting small-molecule permeability for the Mycobacterium tuberculosis cell wall = Computermethoden zur Bestimmung von Protein-Ligand Verweilzeiten in bakteriellen Enoyl-ACP Reduktasen und Vorhersage der Permeabilitätswahrscheinlichkeit kleiner Moleküle gegenüber der Mycobacterium tuberculosis Zellwand |
| title_full | Computational methods for assessing drug-target residence times in bacterial enoyl-ACP reductases and predicting small-molecule permeability for the Mycobacterium tuberculosis cell wall = Computermethoden zur Bestimmung von Protein-Ligand Verweilzeiten in bakteriellen Enoyl-ACP Reduktasen und Vorhersage der Permeabilitätswahrscheinlichkeit kleiner Moleküle gegenüber der Mycobacterium tuberculosis Zellwand vorgelegt von Benjamin Merget aus Aschaffenburg |
| title_fullStr | Computational methods for assessing drug-target residence times in bacterial enoyl-ACP reductases and predicting small-molecule permeability for the Mycobacterium tuberculosis cell wall = Computermethoden zur Bestimmung von Protein-Ligand Verweilzeiten in bakteriellen Enoyl-ACP Reduktasen und Vorhersage der Permeabilitätswahrscheinlichkeit kleiner Moleküle gegenüber der Mycobacterium tuberculosis Zellwand vorgelegt von Benjamin Merget aus Aschaffenburg |
| title_full_unstemmed | Computational methods for assessing drug-target residence times in bacterial enoyl-ACP reductases and predicting small-molecule permeability for the Mycobacterium tuberculosis cell wall = Computermethoden zur Bestimmung von Protein-Ligand Verweilzeiten in bakteriellen Enoyl-ACP Reduktasen und Vorhersage der Permeabilitätswahrscheinlichkeit kleiner Moleküle gegenüber der Mycobacterium tuberculosis Zellwand vorgelegt von Benjamin Merget aus Aschaffenburg |
| title_short | Computational methods for assessing drug-target residence times in bacterial enoyl-ACP reductases and predicting small-molecule permeability for the Mycobacterium tuberculosis cell wall |
| title_sort | computational methods for assessing drug target residence times in bacterial enoyl acp reductases and predicting small molecule permeability for the mycobacterium tuberculosis cell wall computermethoden zur bestimmung von protein ligand verweilzeiten in bakteriellen enoyl acp reduktasen und vorhersage der permeabilitatswahrscheinlichkeit kleiner molekule gegenuber der mycobacterium tuberculosis zellwand |
| title_sub | = Computermethoden zur Bestimmung von Protein-Ligand Verweilzeiten in bakteriellen Enoyl-ACP Reduktasen und Vorhersage der Permeabilitätswahrscheinlichkeit kleiner Moleküle gegenüber der Mycobacterium tuberculosis Zellwand |
| topic | Permeabilität (DE-588)4173828-7 gnd Arzneimitteldesign (DE-588)4278218-1 gnd Molekulardynamik (DE-588)4170370-4 gnd Computational chemistry (DE-588)4290091-8 gnd Enoyl-acyl-carrier-protein-Reductase Enoyl-[acyl-carrier-protein]-Reductase (DE-588)4481400-8 gnd Tuberkelbakterium (DE-588)4186384-7 gnd |
| topic_facet | Permeabilität Arzneimitteldesign Molekulardynamik Computational chemistry Enoyl-acyl-carrier-protein-Reductase Enoyl-[acyl-carrier-protein]-Reductase Tuberkelbakterium Hochschulschrift |
| url | https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-127386 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029610069&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT mergetbenjamin computationalmethodsforassessingdrugtargetresidencetimesinbacterialenoylacpreductasesandpredictingsmallmoleculepermeabilityforthemycobacteriumtuberculosiscellwallcomputermethodenzurbestimmungvonproteinligandverweilzeiteninbakteriellenenoylacpreduktasenund AT mergetbenjamin computermethodenzurbestimmungvonproteinligandverweilzeiteninbakteriellenenoylacpreduktasenundvorhersagederpermeabilitatswahrscheinlichkeitkleinermolekulegegenuberdermycobacteriumtuberculosiszellwand |