Abstract
The mechanisms involved in enzymatic hydride transfer have been studied for years, but questions remain due, in part, to the difficulty of probing the effects of protein motion and hydrogen tunneling. In this study, we use transition path sampling (TPS) with normal mode centroid molecular dynamics (CMD) to calculate the barrier to hydride transfer in yeast alcohol dehydrogenase (YADH) and human heart lactate dehydrogenase (LDH). Calculation of the work applied to the hydride allowed for observation of the change in barrier height upon inclusion of quantum dynamics. Similar calculations were performed using deuterium as the transferring particle in order to approximate kinetic isotope effects (KIEs). The change in barrier height in YADH is indicative of a zero-point energy (ZPE) contribution and is evidence that catalysis occurs via a protein compression that mediates a near-barrierless hydride transfer. Calculation of the KIE using the difference in barrier height between the hydride and deuteride agreed well with experimental results.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1177-1181 |
| Number of pages | 5 |
| Journal | Journal of Physical Chemistry Letters |
| Volume | 6 |
| Issue number | 7 |
| DOIs | |
| State | Published - Apr 2 2015 |
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Keywords
- centroid molecular dynamics (CMD)
- enzymatic hydrogen transfer
- fast protein dynamics
- transition path sampling (TPS)
- tunneling in enzymes
- yeast alcohol dehydrogenase (YADH)
ASJC Scopus subject areas
- Materials Science(all)
Cite this
Another look at the mechanisms of hydride transfer enzymes with quantum and classical transition path sampling. / Dzierlenga, Michael W.; Antoniou, Dimitri; Schwartz, Steven D.
In: Journal of Physical Chemistry Letters, Vol. 6, No. 7, 02.04.2015, p. 1177-1181.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Another look at the mechanisms of hydride transfer enzymes with quantum and classical transition path sampling
AU - Dzierlenga, Michael W.
AU - Antoniou, Dimitri
AU - Schwartz, Steven D
PY - 2015/4/2
Y1 - 2015/4/2
N2 - The mechanisms involved in enzymatic hydride transfer have been studied for years, but questions remain due, in part, to the difficulty of probing the effects of protein motion and hydrogen tunneling. In this study, we use transition path sampling (TPS) with normal mode centroid molecular dynamics (CMD) to calculate the barrier to hydride transfer in yeast alcohol dehydrogenase (YADH) and human heart lactate dehydrogenase (LDH). Calculation of the work applied to the hydride allowed for observation of the change in barrier height upon inclusion of quantum dynamics. Similar calculations were performed using deuterium as the transferring particle in order to approximate kinetic isotope effects (KIEs). The change in barrier height in YADH is indicative of a zero-point energy (ZPE) contribution and is evidence that catalysis occurs via a protein compression that mediates a near-barrierless hydride transfer. Calculation of the KIE using the difference in barrier height between the hydride and deuteride agreed well with experimental results.
AB - The mechanisms involved in enzymatic hydride transfer have been studied for years, but questions remain due, in part, to the difficulty of probing the effects of protein motion and hydrogen tunneling. In this study, we use transition path sampling (TPS) with normal mode centroid molecular dynamics (CMD) to calculate the barrier to hydride transfer in yeast alcohol dehydrogenase (YADH) and human heart lactate dehydrogenase (LDH). Calculation of the work applied to the hydride allowed for observation of the change in barrier height upon inclusion of quantum dynamics. Similar calculations were performed using deuterium as the transferring particle in order to approximate kinetic isotope effects (KIEs). The change in barrier height in YADH is indicative of a zero-point energy (ZPE) contribution and is evidence that catalysis occurs via a protein compression that mediates a near-barrierless hydride transfer. Calculation of the KIE using the difference in barrier height between the hydride and deuteride agreed well with experimental results.
KW - centroid molecular dynamics (CMD)
KW - enzymatic hydrogen transfer
KW - fast protein dynamics
KW - transition path sampling (TPS)
KW - tunneling in enzymes
KW - yeast alcohol dehydrogenase (YADH)
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UR - http://www.scopus.com/inward/citedby.url?scp=84926647779&partnerID=8YFLogxK
U2 - 10.1021/acs.jpclett.5b00346
DO - 10.1021/acs.jpclett.5b00346
M3 - Article
C2 - 26262969
AN - SCOPUS:84926647779
VL - 6
SP - 1177
EP - 1181
JO - Journal of Physical Chemistry Letters
JF - Journal of Physical Chemistry Letters
SN - 1948-7185
IS - 7
ER -