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General transition-state force field for cytochrome p450 Hydroxylation

Rydberg, Patrik LU ; Olsen, Lars; Norrby, Per-Ola and Ryde, Ulf LU (2007) In Journal of Chemical Theory and Computation 3(5). p.1765-1773
Abstract
We have developed force-field parameters for the hydrogen-abstraction transition state of aliphatic hydroxylation by cytochrome P450 using the Q2MM approach. The parametrization is based on quantum chemical (B3LYP) transition-state structures and Hessian matrices for 24 diverse substrate models (14 in the training set and 10 in the test set). The force field is intended to be applicable to any druglike molecule by the use of the general Amber force field (GAFF) for the substrates. The parameters reproduce the geometries within 0.1 angstrom and 1.2 degrees for bond lengths and angles, respectively, with no significant differences between the training and test sets. The Hessian matrix is also well reproduced with a correlation coefficient of... (More)
We have developed force-field parameters for the hydrogen-abstraction transition state of aliphatic hydroxylation by cytochrome P450 using the Q2MM approach. The parametrization is based on quantum chemical (B3LYP) transition-state structures and Hessian matrices for 24 diverse substrate models (14 in the training set and 10 in the test set). The force field is intended to be applicable to any druglike molecule by the use of the general Amber force field (GAFF) for the substrates. The parameters reproduce the geometries within 0.1 angstrom and 1.2 degrees for bond lengths and angles, respectively, with no significant differences between the training and test sets. The Hessian matrix is also well reproduced with a correlation coefficient of 0.99. The parametrization is performed by the ideal iterative approach of Norrby and Liljefors, which we have implemented for the Amber software. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Chemical Theory and Computation
volume
3
issue
5
pages
1765 - 1773
publisher
The American Chemical Society
external identifiers
  • wos:000249454500012
  • scopus:35948961951
ISSN
1549-9618
DOI
10.1021/ct700110f
language
English
LU publication?
yes
id
daf44db2-e503-4cb0-b4b6-779b388b394e (old id 657319)
date added to LUP
2007-12-21 13:59:11
date last changed
2017-06-11 03:28:39
@article{daf44db2-e503-4cb0-b4b6-779b388b394e,
  abstract     = {We have developed force-field parameters for the hydrogen-abstraction transition state of aliphatic hydroxylation by cytochrome P450 using the Q2MM approach. The parametrization is based on quantum chemical (B3LYP) transition-state structures and Hessian matrices for 24 diverse substrate models (14 in the training set and 10 in the test set). The force field is intended to be applicable to any druglike molecule by the use of the general Amber force field (GAFF) for the substrates. The parameters reproduce the geometries within 0.1 angstrom and 1.2 degrees for bond lengths and angles, respectively, with no significant differences between the training and test sets. The Hessian matrix is also well reproduced with a correlation coefficient of 0.99. The parametrization is performed by the ideal iterative approach of Norrby and Liljefors, which we have implemented for the Amber software.},
  author       = {Rydberg, Patrik and Olsen, Lars and Norrby, Per-Ola and Ryde, Ulf},
  issn         = {1549-9618},
  language     = {eng},
  number       = {5},
  pages        = {1765--1773},
  publisher    = {The American Chemical Society},
  series       = {Journal of Chemical Theory and Computation},
  title        = {General transition-state force field for cytochrome p450 Hydroxylation},
  url          = {http://dx.doi.org/10.1021/ct700110f},
  volume       = {3},
  year         = {2007},
}