Solvating, manipulating, damaging, and repairing DNA in a computer

Bunta, Juraj Kotulic; Dahlberg, Martin; Eriksson, Leif A.; Korolev, Nikolay; Laaksonen, Aatto; Lohikoski, Raimo A.; Lyubartsev, Alexander P.; Pinák, Miroslav; Schyman, Patric

doi:10.1002/qua.21191

Cited by 3 publications

(2 citation statements)

References 73 publications

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“…These studies complement other work in the literature that typically focused on the effect of charge (for example, protonation, hydrogen bonding, or metal binding) on glycosidic bond stability, either implicitly through measuring changes in acidities − or glycosidic bond length, − or explicitly through barrier height determination. − Additional small model studies have included features of particular enzyme active sites, for example, hOgg1, − hUNG2, hNEIL, , and hTDG . Large model studies of enzymatic deglycosylation have combined the various small model observations to gain further insight into how the different features work together. − Combined, this body of research has provided qualitative explanations for the relative base excision rates observed in biological systems.…”

Section: Introductionmentioning

confidence: 78%

Glycosidic Bond Cleavage in Deoxynucleotides: Effects of Solvent and the DNA Phosphate Backbone in the Computational Model

2012

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Density functional theory (B3LYP) was employed to examine the hydrolysis of the canonical 2'-deoxynucleotides in varied environments (gas phase or water) using different computational models for the sugar residue (methyl or phosphate group at C5') and nucleophile (water activated through full or partial proton abstraction). Regardless of the degree of nucleophile activation, our results show that key geometrical parameters along the reaction pathway are notably altered upon direct inclusion of solvent effects in the optimization routine, which leads to significant changes in the reaction energetics and better agreement with experiment. Therefore, despite the wide use of gas-phase calculations in the literature, small model computational work, as well as large-scale enzyme models, that strive to understand nucleotide deglycosylation must adequately describe the environment. Alternatively, although inclusion of the phosphate group at C5' also affects the geometries of important stationary points, the effects cancel to yield unchanged deglycosylation barriers, and therefore smaller computational models can be used to estimate the energy associated with nucleotide deglycosylation, with the 5' phosphate group included if full (geometric) details of the reaction are desired. Hydrogen-bonding interactions with the nucleobase can significantly reduce the barrier to deglycosylation, which supports suggestions that discrete hydrogen-bonding interactions with active-site amino acid residues can play a significant role in enzyme-catalyzed nucleobase excision. Taken together with previous studies, the present work provides vital clues about the components that must be included in future studies of the deglycosylation of isolated noncanonical nucleotides, as well as the corresponding enzyme-catalyzed reactions.

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Section: Introductionmentioning

confidence: 78%

Glycosidic Bond Cleavage in Deoxynucleotides: Effects of Solvent and the DNA Phosphate Backbone in the Computational Model

2012

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“…Proper treatment of these interactions, together with the developments of Force Fields designed for explicit solvent models (Cornell et al, 1995;MacKerell et al, 1995;MacKerell, 2004) and advances in computer power have lead to large use of molecular dynamic simulations in the study of nucleic acids. Here we focus on the modeling, at different levels of sophistication, of nucleic acids in physiological environments with different species of counterion, either mono and multivalent ( (Lyubartsev & Laaksonen, 1998b;van Dam et al, 1998;Mocci et al, 2004;Bunta et al, 2007;Korolev et al, 2001Korolev et al, , 2002Korolev et al, , 2004aKorolev et al, , 2004b and we give some examples of how the MD trajectories can be analyzed and the results checked against experimental data using M.DynaMix software.…”

Section: Hydration and Coordination Of Counterions Around Dnamentioning

confidence: 99%

M.DynaMix Studies of Solvation, Solubility and Permeability

Laaksonen¹,

Lyubartsev²,

Mocci³

2012

Molecular Dynamics - Studies of Synthetic and Biological Macromolecules

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Molecular Dynamics is a two-volume compendium of the ever-growing applications of molecular dynamics simulations to solve a wider range of scientific and engineering challenges. The contents illustrate the rapid progress on molecular dynamics simulations in many fields of science and technology, such as nanotechnology, energy research, and biology, due to the advances of new dynamics theories and the extraordinary power of today's computers. This second book begins with an introduction of molecular dynamics simulations to macromolecules and then illustrates the computer experiments using molecular dynamics simulations in the studies of synthetic and biological macromolecules, plasmas, and nanomachines. Coverage of this book includes: Complex formation and dynamics of polymers Dynamics of lipid bilayers, peptides, DNA, RNA, and proteins Complex liquids and plasmas Dynamics of molecules on surfaces Nanofluidics and nanomachines How to referenceIn order to correctly reference this scholarly work, feel free to copy and paste the following:

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Molecular Mechanisms of DNA Replication and Repair Machinery: Insights from Microscopic Simulations

Chou

Aksimentiev

2019

Advcd Theory and Sims

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Reproduction, the hallmark of biological activity, requires making an accurate copy of the genetic material to allow the progeny to inherit parental traits. In all living cells, the process of DNA replication is carried out by a concerted action of multiple protein species forming a loose protein-nucleic acid complex, the replisome. Proofreading and error correction generally accompany replication but also occur independently, safeguarding genetic information through all phases of the cell cycle. Advances in biochemical characterization of intracellular processes, proteomics, and the advent of single-molecule biophysics have brought about a treasure trove of information awaiting to be assembled into an accurate mechanistic model of the DNA replication process. This review describes recent efforts to model elements of DNA replication and repair processes using computer simulations, an approach that has gained immense popularity in many areas of molecular biophysics but has yet to become mainstream in the DNA metabolism community. It highlights the use of diverse computational methods to address specific problems of the fields and discusses unexplored possibilities that lie ahead for the computational approaches in these areas.

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Solvating, manipulating, damaging, and repairing DNA in a computer

Cited by 3 publications

References 73 publications

Glycosidic Bond Cleavage in Deoxynucleotides: Effects of Solvent and the DNA Phosphate Backbone in the Computational Model

Glycosidic Bond Cleavage in Deoxynucleotides: Effects of Solvent and the DNA Phosphate Backbone in the Computational Model

M.DynaMix Studies of Solvation, Solubility and Permeability

Molecular Mechanisms of DNA Replication and Repair Machinery: Insights from Microscopic Simulations

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