How amide hydrogens exchange in native proteins.
(2015) In Proceedings of the National Academy of Sciences 112(33). p.10383-10388- Abstract
- Amide hydrogen exchange (HX) is widely used in protein biophysics even though our ignorance about the HX mechanism makes data interpretation imprecise. Notably, the open exchange-competent conformational state has not been identified. Based on analysis of an ultralong molecular dynamics trajectory of the protein BPTI, we propose that the open (O) states for amides that exchange by subglobal fluctuations are locally distorted conformations with two water molecules directly coordinated to the N-H group. The HX protection factors computed from the relative O-state populations agree well with experiment. The O states of different amides show little or no temporal correlation, even if adjacent residues unfold cooperatively. The mean residence... (More)
- Amide hydrogen exchange (HX) is widely used in protein biophysics even though our ignorance about the HX mechanism makes data interpretation imprecise. Notably, the open exchange-competent conformational state has not been identified. Based on analysis of an ultralong molecular dynamics trajectory of the protein BPTI, we propose that the open (O) states for amides that exchange by subglobal fluctuations are locally distorted conformations with two water molecules directly coordinated to the N-H group. The HX protection factors computed from the relative O-state populations agree well with experiment. The O states of different amides show little or no temporal correlation, even if adjacent residues unfold cooperatively. The mean residence time of the O state is ∼100 ps for all examined amides, so the large variation in measured HX rate must be attributed to the opening frequency. A few amides gain solvent access via tunnels or pores penetrated by water chains including native internal water molecules, but most amides access solvent by more local structural distortions. In either case, we argue that an overcoordinated N-H group is necessary for efficient proton transfer by Grotthuss-type structural diffusion. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/7733042
- author
- Persson, Filip LU and Halle, Bertil LU
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Proceedings of the National Academy of Sciences
- volume
- 112
- issue
- 33
- pages
- 10383 - 10388
- publisher
- National Academy of Sciences
- external identifiers
-
- pmid:26195754
- wos:000359738300071
- scopus:84939817161
- pmid:26195754
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.1506079112
- language
- English
- LU publication?
- yes
- id
- 1b737a2d-6938-4431-aab4-d03020f0a362 (old id 7733042)
- date added to LUP
- 2016-04-01 10:11:32
- date last changed
- 2022-04-12 02:56:16
@article{1b737a2d-6938-4431-aab4-d03020f0a362,
abstract = {{Amide hydrogen exchange (HX) is widely used in protein biophysics even though our ignorance about the HX mechanism makes data interpretation imprecise. Notably, the open exchange-competent conformational state has not been identified. Based on analysis of an ultralong molecular dynamics trajectory of the protein BPTI, we propose that the open (O) states for amides that exchange by subglobal fluctuations are locally distorted conformations with two water molecules directly coordinated to the N-H group. The HX protection factors computed from the relative O-state populations agree well with experiment. The O states of different amides show little or no temporal correlation, even if adjacent residues unfold cooperatively. The mean residence time of the O state is ∼100 ps for all examined amides, so the large variation in measured HX rate must be attributed to the opening frequency. A few amides gain solvent access via tunnels or pores penetrated by water chains including native internal water molecules, but most amides access solvent by more local structural distortions. In either case, we argue that an overcoordinated N-H group is necessary for efficient proton transfer by Grotthuss-type structural diffusion.}},
author = {{Persson, Filip and Halle, Bertil}},
issn = {{1091-6490}},
language = {{eng}},
number = {{33}},
pages = {{10383--10388}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences}},
title = {{How amide hydrogens exchange in native proteins.}},
url = {{http://dx.doi.org/10.1073/pnas.1506079112}},
doi = {{10.1073/pnas.1506079112}},
volume = {{112}},
year = {{2015}},
}