|
|
|
|
| LEADER |
01000caa a22002652 4500 |
| 001 |
NLM240247086 |
| 003 |
DE-627 |
| 005 |
20240504231924.0 |
| 007 |
cr uuu---uuuuu |
| 008 |
231224s2014 xx |||||o 00| ||eng c |
| 024 |
7 |
|
|a 10.1002/jcc.23680
|2 doi
|
| 028 |
5 |
2 |
|a pubmed24n1397.xml
|
| 035 |
|
|
|a (DE-627)NLM240247086
|
| 035 |
|
|
|a (NLM)25043499
|
| 040 |
|
|
|a DE-627
|b ger
|c DE-627
|e rakwb
|
| 041 |
|
|
|a eng
|
| 100 |
1 |
|
|a Kingsley, Laura J
|e verfasserin
|4 aut
|
| 245 |
1 |
0 |
|a Including ligand-induced protein flexibility into protein tunnel prediction
|
| 264 |
|
1 |
|c 2014
|
| 336 |
|
|
|a Text
|b txt
|2 rdacontent
|
| 337 |
|
|
|a ƒaComputermedien
|b c
|2 rdamedia
|
| 338 |
|
|
|a ƒa Online-Ressource
|b cr
|2 rdacarrier
|
| 500 |
|
|
|a Date Completed 12.05.2015
|
| 500 |
|
|
|a Date Revised 04.05.2024
|
| 500 |
|
|
|a published: Print-Electronic
|
| 500 |
|
|
|a Citation Status MEDLINE
|
| 520 |
|
|
|a © 2014 Wiley Periodicals, Inc.
|
| 520 |
|
|
|a In proteins with buried active sites, understanding how ligands migrate through the tunnels that connect the exterior of the protein to the active site can shed light on substrate specificity and enzyme function. A growing body of evidence highlights the importance of protein flexibility in the binding site on ligand binding; however, the influence of protein flexibility throughout the body of the protein during ligand entry and egress is much less characterized. We have developed a novel tunnel prediction and evaluation method named IterTunnel, which includes the influence of ligand-induced protein flexibility, guarantees ligand egress, and provides detailed free energy information as the ligand proceeds along the egress route. IterTunnel combines geometric tunnel prediction with steered molecular dynamics in an iterative process to identify tunnels that open as a result of ligand migration and calculates the potential of mean force of ligand egress through a given tunnel. Applying this new method to cytochrome P450 2B6, we demonstrate the influence of protein flexibility on the shape and accessibility of tunnels. More importantly, we demonstrate that the ligand itself, while traversing through a tunnel, can reshape tunnels due to its interaction with the protein. This process results in the exposure of new tunnels and the closure of preexisting tunnels as the ligand migrates from the active site
|
| 650 |
|
4 |
|a Journal Article
|
| 650 |
|
4 |
|a Research Support, N.I.H., Extramural
|
| 650 |
|
4 |
|a Research Support, U.S. Gov't, Non-P.H.S.
|
| 650 |
|
4 |
|a conformational ensemble
|
| 650 |
|
4 |
|a cytochrome P450 2B6
|
| 650 |
|
4 |
|a induced fit
|
| 650 |
|
4 |
|a potential of mean force
|
| 650 |
|
4 |
|a protein flexibility
|
| 650 |
|
4 |
|a steered molecular dynamics
|
| 650 |
|
4 |
|a tunnel prediction
|
| 650 |
|
4 |
|a umbrella sampling
|
| 650 |
|
7 |
|a 1-(4-chlorophenyl)imidazole
|2 NLM
|
| 650 |
|
7 |
|a Imidazoles
|2 NLM
|
| 650 |
|
7 |
|a Ligands
|2 NLM
|
| 650 |
|
7 |
|a CYP2B6 protein, human
|2 NLM
|
| 650 |
|
7 |
|a EC 1.14.14.1
|2 NLM
|
| 650 |
|
7 |
|a Cytochrome P-450 CYP2B6
|2 NLM
|
| 650 |
|
7 |
|a EC 1.14.14.1
|2 NLM
|
| 700 |
1 |
|
|a Lill, Markus A
|e verfasserin
|4 aut
|
| 773 |
0 |
8 |
|i Enthalten in
|t Journal of computational chemistry
|d 1984
|g 35(2014), 24 vom: 15. Sept., Seite 1748-56
|w (DE-627)NLM098138448
|x 1096-987X
|7 nnns
|
| 773 |
1 |
8 |
|g volume:35
|g year:2014
|g number:24
|g day:15
|g month:09
|g pages:1748-56
|
| 856 |
4 |
0 |
|u http://dx.doi.org/10.1002/jcc.23680
|3 Volltext
|
| 912 |
|
|
|a GBV_USEFLAG_A
|
| 912 |
|
|
|a SYSFLAG_A
|
| 912 |
|
|
|a GBV_NLM
|
| 912 |
|
|
|a GBV_ILN_350
|
| 951 |
|
|
|a AR
|
| 952 |
|
|
|d 35
|j 2014
|e 24
|b 15
|c 09
|h 1748-56
|