Internal coordinate modeling of DNA: Force field comparisons

Flatters, Delphine; Zakrzewska, K.; Lavery, Richard

doi:10.1002/(sici)1096-987x(199706)18:8<1043::aid-jcc8>3.3.co;2-y

Cited by 5 publications

(7 citation statements)

References 8 publications

(10 reference statements)

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“…Moving beyond statistical considerations, there have been several attempts to explore the conformation and energetics of DNA, using a variety of both backbone torsion angles and helicoidal parameters as effective degrees of freedom (12–15). For example, a study of the energetics of base stacking (16) replaced the backbone with methyl groups at the C1′ atoms.…”

Section: Introductionmentioning

confidence: 99%

The physical determinants of the DNA conformational landscape: an analysis of the potential energy surface of single-strand dinucleotides in the conformational space of duplex DNA

Elsawy

2005

Nucleic Acids Research

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A multivariate analysis of the backbone and sugar torsion angles of dinucleotide fragments was used to construct a 3D principal conformational subspace (PCS) of DNA duplex crystal structures. The potential energy surface (PES) within the PCS was mapped for a single-strand dinucleotide model using an empirical energy function. The low energy regions of the surface encompass known DNA forms and also identify previously unclassified conformers. The physical determinants of the conformational landscape are found to be predominantly steric interactions within the dinucleotide backbone, with medium-dependent backbone-base electrostatic interactions serving to tune the relative stability of the different local energy minima. The fidelity of the PES to duplex DNA properties is validated through a correspondence to the conformational distribution of duplex DNA crystal structures and the reproduction of observed sequence specific propensities for the formation of A-form DNA. The utility of the PES is demonstrated through its succinct and accurate description of complex conformational processes in simulations of duplex DNA. The study suggests that stereochemical considerations of the nucleic acid backbone play a role in determining conformational preferences of DNA which is analogous to the role of local steric interactions in determining polypeptide secondary structure.

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Section: Introductionmentioning

confidence: 99%

The physical determinants of the DNA conformational landscape: an analysis of the potential energy surface of single-strand dinucleotides in the conformational space of duplex DNA

Elsawy

2005

Nucleic Acids Research

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“…Another alternative is FLEX, implemented in the program JUMNA, which may be considered a knowledge-based force field for nucleic acids. 255,256 JUMNA includes an internal coordinate representation of DNA, treating solvation with a sigmoidal dielectric screening term rather than with an explicit solvent model. Accordingly, JUMNA allows for conformational studies on oligonucleotides that are significantly larger than that currently accessible to all-atom, explicit solvent representations.…”

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confidence: 99%

Empirical force fields for biological macromolecules: Overview and issues

2004

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Empirical force field-based studies of biological macromolecules are becoming a common tool for investigating their structure-activity relationships at an atomic level of detail. Such studies facilitate interpretation of experimental data and allow for information not readily accessible to experimental methods to be obtained. A large part of the success of empirical force field-based methods is the quality of the force fields combined with the algorithmic advances that allow for more accurate reproduction of experimental observables. Presented is an overview of the issues associated with the development and application of empirical force fields to biomolecular systems. This is followed by a summary of the force fields commonly applied to the different classes of biomolecules; proteins, nucleic acids, lipids, and carbohydrates. In addition, issues associated with computational studies on "heterogeneous" biomolecular systems and the transferability of force fields to a wide range of organic molecules of pharmacological interest are discussed.

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“…More recently, increases in computer power have led to the incorporation of more accurate and implicit solvent models, such as finite difference Poisson‐Boltzmann methods (Zacharias and Sklenar, ). Although it is not directly possible to mix and match the internal coordinate force fields with those designed for all‐atom simulation, the FLEX force field has been shown to agree well with the all‐atom nucleic acid force field described by Cornell et al () and Flatters et al (). For more information on the differences between internal coordinate and all‐atom representations, see UNIT .…”

Section: Issues In the Simulation Of Nucleic Acidsmentioning

confidence: 84%

Molecular Modeling of Nucleic Acid Structure: Setup and Analysis

Cheatham

Brooks

Kollman

2001

CP Nucleic Acid Chemistry

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The last in a set of units by these authors, this unit addresses some important remaining questions about molecular modeling of nucleic acids. It describes how to choose an appropriate molecular mechanics force field; how to set up and equilibrate the system for accurate simulation of a nucleic acid in an explicit solvent by molecular dynamics or Monte Carlo simulation; and provides some information about how to analyze molecular dynamics trajectories. ISSUES WITH SIMULATING NUCLEIC ACIDSFrom the information presented in previous units (UNITS 7.5, 7.8 & 7.9), one should have a reasonable understanding of the various trade-offs that are necessary to model nucleic acid structures. For instance, when choosing an energy representation and a means to sample relevant conformations, there is a tradeoff between detail, sampling, and computational cost. Although the discussions thus far have presented basic means for modeling nucleic acids, some important details have not been sufficiently addressed. Reasonable decisions that remain for the prospective modeler to address are: (1) which empirical molecular mechanical force field is appropriate; (2) if one wants to run an accurate simulation of a nucleic acid in an explicit solvent, how does one set up and equilibrate the system; (3) how long should the production time of the simulation be in order to see convergence in properties of interest; and (4) how does one analyze molecular dynamics trajectories? This unit provides the answers to some of these questions and outlines a protocol for accurate simulation of nucleic acids.

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Internal coordinate modeling of DNA: Force field comparisons

Cited by 5 publications

References 8 publications

The physical determinants of the DNA conformational landscape: an analysis of the potential energy surface of single-strand dinucleotides in the conformational space of duplex DNA

The physical determinants of the DNA conformational landscape: an analysis of the potential energy surface of single-strand dinucleotides in the conformational space of duplex DNA

Empirical force fields for biological macromolecules: Overview and issues

Molecular Modeling of Nucleic Acid Structure: Setup and Analysis

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