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. However, 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 mechanically 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(sp(3))-N(sp(2)) bond. The pseudobond parameters were optimized on a training set of 10 molecules representing several nucleotide 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 properties, 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 nucleoside 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.
authors: Department of Chemistry, Duke University, 124 Science Drive, 5301 French Science Center, Durham, North Carolina 27708-0346, USA.
authors: Robin
authors: R
authors: Chaudret
authors: Jerry M
authors: JM
authors: Parks
authors: Weitao
authors: W
authors: Yang
mesh_terms: D056004:Molecular Dynamics Simulation; D009705:Nucleosides / Q000737:chemistry*; D009711:Nucleotides / Q000737:chemistry*; D011789:Quantum Theory
chemical_list: D009705:Nucleosides; D009711:Nucleotides
references: Science. 2004 Jan 9;303(5655):186-95
references: 14716003
references: J Chem Phys. 2006 Feb 28;124(8):084107
references: 16512708
references: Chemphyschem. 2005 Sep 5;6(9):1853-65
references: 16086343
references: J Comput Chem. 2002 Apr 30;23(6):610-24
references: 11939595
references: J Mol Biol. 1976 May 15;103(2):227-49
references: 985660
references: J Chem Phys. 2005 Jan 8;122(2):024114
references: 15638579
references: Phys Rev B Condens Matter. 1988 Jan 15;37(2):785-789
references: 9944570
references: J Comput Chem. 2008 Jul 15;29(9):1440-9
references: 18293309
references: Acc Chem Res. 2010 Jan 19;43(1):142-51
references: 19728702
references: J Phys Chem B. 2012 Jun 14;116(23):6889-97
references: 22417185
references: J Comput Chem. 2002 Jan 15;23(1):48-58
references: 11913389
references: J Chem Phys. 2008 Oct 21;129(15):154106
references: 19045175
references: Annu Rev Phys Chem. 2008;59:573-601
references: 18393679
references: J Phys Condens Matter. 2010 Oct 20;22(41):413101
references: 21386583
references: Angew Chem Int Ed Engl. 2009;48(7):1198-229
references: 19173328
references: Theochem. 2009 Mar 30;898(1-3):17-30
references: 24146439