Challenges and advances in the computational modeling of biological phosphate hydrolysis
Petrović, Dušan ; Szeler, Klaudia and Kamerlin, Shina Caroline Lynn LU
(2018)
In Chemical Communications
54(25).
p.3077-3089
- Abstract
Phosphate ester hydrolysis is fundamental to many life processes, and has been the topic of substantial experimental and computational research effort. However, even the simplest of phosphate esters can be hydrolyzed through multiple possible pathways that can be difficult to distinguish between, either experimentally, or computationally. Therefore, the mechanisms of both the enzymatic and non-enzymatic reactions have been historically controversial. In the present contribution, we highlight a number of technical issues involved in reliably modeling these computationally challenging reactions, as well as proposing potential solutions. We also showcase examples of our own work in this area, discussing both the non-enzymatic reaction in... (More)
Phosphate ester hydrolysis is fundamental to many life processes, and has been the topic of substantial experimental and computational research effort. However, even the simplest of phosphate esters can be hydrolyzed through multiple possible pathways that can be difficult to distinguish between, either experimentally, or computationally. Therefore, the mechanisms of both the enzymatic and non-enzymatic reactions have been historically controversial. In the present contribution, we highlight a number of technical issues involved in reliably modeling these computationally challenging reactions, as well as proposing potential solutions. We also showcase examples of our own work in this area, discussing both the non-enzymatic reaction in aqueous solution, as well as insights obtained from the computational modeling of organophosphate hydrolysis and catalytic promiscuity amongst enzymes that catalyze phosphoryl transfer.
(Less)
- author
- Petrović, Dušan
; Szeler, Klaudia
and Kamerlin, Shina Caroline Lynn
LU
- publishing date
- 2018-03-28
- type
- Contribution to journal
- publication status
- published
- keywords
- Alkaline Phosphatase/metabolism, Biocatalysis, Computer Simulation, Hydrolysis, Models, Molecular, Molecular Structure, Organophosphates/chemistry, Phosphates/chemistry, Quantum Theory
- in
- Chemical Communications
- volume
- 54
- issue
- 25
- pages
- 13 pages
- publisher
- Royal Society of Chemistry
- external identifiers
-
- pmid:29412205
- scopus:85044324608
- ISSN
- 1364-548X
- DOI
- 10.1039/c7cc09504j
- language
- English
- LU publication?
- no
- id
- 0de1ded7-e79a-4a5c-a610-f7f9a0d9f0f1
- date added to LUP
- 2025-01-11 21:18:39
- date last changed
- 2025-06-15 16:04:15
@article{0de1ded7-e79a-4a5c-a610-f7f9a0d9f0f1,
abstract = {{<p>Phosphate ester hydrolysis is fundamental to many life processes, and has been the topic of substantial experimental and computational research effort. However, even the simplest of phosphate esters can be hydrolyzed through multiple possible pathways that can be difficult to distinguish between, either experimentally, or computationally. Therefore, the mechanisms of both the enzymatic and non-enzymatic reactions have been historically controversial. In the present contribution, we highlight a number of technical issues involved in reliably modeling these computationally challenging reactions, as well as proposing potential solutions. We also showcase examples of our own work in this area, discussing both the non-enzymatic reaction in aqueous solution, as well as insights obtained from the computational modeling of organophosphate hydrolysis and catalytic promiscuity amongst enzymes that catalyze phosphoryl transfer.</p>}},
author = {{Petrović, Dušan and Szeler, Klaudia and Kamerlin, Shina Caroline Lynn}},
issn = {{1364-548X}},
keywords = {{Alkaline Phosphatase/metabolism; Biocatalysis; Computer Simulation; Hydrolysis; Models, Molecular; Molecular Structure; Organophosphates/chemistry; Phosphates/chemistry; Quantum Theory}},
language = {{eng}},
month = {{03}},
number = {{25}},
pages = {{3077--3089}},
publisher = {{Royal Society of Chemistry}},
series = {{Chemical Communications}},
title = {{Challenges and advances in the computational modeling of biological phosphate hydrolysis}},
url = {{http://dx.doi.org/10.1039/c7cc09504j}},
doi = {{10.1039/c7cc09504j}},
volume = {{54}},
year = {{2018}},
}