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Title: Pseudobond parameters for QM/MM studies involving nucleosides, nucleotides, and their analogs

Abstract

In biological systems involving nucleosides, nucleotides, or their respective analogs, the ribose sugar moiety is the most common reaction site, for example, during DNA replication and repair. How- ever, nucleic bases, which comprise a sizable portion of nucleotide molecules, are usually unreactive during such processes. In quantum mechanical/molecular simulations of nucleic acid reactivity, it may therefore be advantageous to describe specific ribosyl or ribosyl phosphate groups quantum me- chanically and their respective nucleic bases with a molecular mechanics potential function. Here, we have extended the pseudobond approach to enable quantum mechanical/molecular mechanical simulations involving nucleotides, nucleosides, and their analogs in which the interface between the two subsystems is located between the sugar and the base, namely, the C(sp3)–N(sp2) bond. The pseudobond parameters were optimized on a training set of 10 molecules representing several nu- cleotide and nucleoside bases and analogs, and they were then tested on a larger test set of 20 diverse molecules. Particular emphasis was placed on providing accurate geometries and electrostatic prop- erties, including electrostatic potential, natural bond orbital (NBO) and atoms in molecules (AIM) charges and AIM first moments. We also tested the optimized parameters on five nucleotide and nu- cleoside analogues of pharmaceutical relevance andmore » a small polypeptide (triglycine). Accuracy was maintained for these systems, which highlights the generality and transferability of the pseudobond approach. © 2013 American Institute of Physics. [http://dx.doi.org/10.1063/1.4772182]« less

Authors:
 [1]; ORCiD logo [2];  [1]
  1. Duke University
  2. ORNL
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1083742
DOE Contract Number:  
AC05-00OR22725
Resource Type:
Journal Article
Journal Name:
Journal of Chemical Physics
Additional Journal Information:
Journal Volume: 138; Journal Issue: 4; Journal ID: ISSN 0021-9606
Country of Publication:
United States
Language:
English
Subject:
QM/MM; simulation

Citation Formats

Chaudret, Robin, Parks, Jerry M., and Yang, Weitao. Pseudobond parameters for QM/MM studies involving nucleosides, nucleotides, and their analogs. United States: N. p., 2013. Web. doi:10.1063/1.4772182.
Chaudret, Robin, Parks, Jerry M., & Yang, Weitao. Pseudobond parameters for QM/MM studies involving nucleosides, nucleotides, and their analogs. United States. doi:10.1063/1.4772182.
Chaudret, Robin, Parks, Jerry M., and Yang, Weitao. Tue . "Pseudobond parameters for QM/MM studies involving nucleosides, nucleotides, and their analogs". United States. doi:10.1063/1.4772182.
@article{osti_1083742,
title = {Pseudobond parameters for QM/MM studies involving nucleosides, nucleotides, and their analogs},
author = {Chaudret, Robin and Parks, Jerry M. and Yang, Weitao},
abstractNote = {In biological systems involving nucleosides, nucleotides, or their respective analogs, the ribose sugar moiety is the most common reaction site, for example, during DNA replication and repair. How- ever, nucleic bases, which comprise a sizable portion of nucleotide molecules, are usually unreactive during such processes. In quantum mechanical/molecular simulations of nucleic acid reactivity, it may therefore be advantageous to describe specific ribosyl or ribosyl phosphate groups quantum me- chanically and their respective nucleic bases with a molecular mechanics potential function. Here, we have extended the pseudobond approach to enable quantum mechanical/molecular mechanical simulations involving nucleotides, nucleosides, and their analogs in which the interface between the two subsystems is located between the sugar and the base, namely, the C(sp3)–N(sp2) bond. The pseudobond parameters were optimized on a training set of 10 molecules representing several nu- cleotide and nucleoside bases and analogs, and they were then tested on a larger test set of 20 diverse molecules. Particular emphasis was placed on providing accurate geometries and electrostatic prop- erties, including electrostatic potential, natural bond orbital (NBO) and atoms in molecules (AIM) charges and AIM first moments. We also tested the optimized parameters on five nucleotide and nu- cleoside analogues of pharmaceutical relevance and a small polypeptide (triglycine). Accuracy was maintained for these systems, which highlights the generality and transferability of the pseudobond approach. © 2013 American Institute of Physics. [http://dx.doi.org/10.1063/1.4772182]},
doi = {10.1063/1.4772182},
journal = {Journal of Chemical Physics},
issn = {0021-9606},
number = 4,
volume = 138,
place = {United States},
year = {2013},
month = {1}
}

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