Emmanuel Giudice

Publications (9)53.16 Total impact

• Source

  Available from: ncbi.nlm.nih.gov

  Article: Molecular dynamics simulations of the 136 unique tetranucleotide sequences of DNA oligonucleotides. II: sequence context effects on the dynamical structures of the 10 unique dinucleotide steps.

  Surjit B Dixit, David L Beveridge, David A Case, Thomas E Cheatham, Emmanuel Giudice, Filip Lankas, Richard Lavery, John H Maddocks, Roman Osman, Heinz Sklenar, Kelly M Thayer, Péter Varnai
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  ABSTRACT: Molecular dynamics (MD) simulations including water and counterions on B-DNA oligomers containing all 136 unique tetranucleotide basepair steps are reported. The objective is to obtain the calculated dynamical structure for at least two copies of each case, use the results to examine issues with regard to convergence and dynamical stability of MD on DNA, and determine the significance of sequence context effects on all unique dinucleotide steps. This information is essential to understand sequence effects on DNA structure and has implications on diverse problems in the structural biology of DNA. Calculations were carried out on the 136 cases embedded in 39 DNA oligomers with repeating tetranucleotide sequences, capped on both ends by GC pairs and each having a total length of 15 nucleotide pairs. All simulations were carried out using a well-defined state-of-the-art MD protocol, the AMBER suite of programs, and the parm94 force field. In a previous article (Beveridge et al. 2004. Biophysical Journal. 87:3799-3813), the research design, details of the simulation protocol, and informatics issues were described. Preliminary results from 15 ns MD trajectories were presented for the d(CpG) step in all 10 unique sequence contexts. The results indicated the sequence context effects to be small for this step, but revealed that MD on DNA at this length of trajectory is subject to surprisingly persistent cooperative transitions of the sugar-phosphate backbone torsion angles alpha and gamma. In this article, we report detailed analysis of the entire trajectory database and occurrence of various conformational substates and its impact on studies of context effects. The analysis reveals a possible direct correspondence between the sequence-dependent dynamical tendencies of DNA structure and the tendency to undergo transitions that "trap" them in nonstandard conformational substates. The difference in mean of the observed basepair step helicoidal parameter distribution with different flanking sequence sometimes differs by as much as one standard deviation, indicating that the extent of sequence effects could be significant. The observations reveal that the impact of a flexible dinucleotide such as CpG could extend beyond the immediate basepair neighbors. The results in general provide new insight into MD on DNA and the sequence-dependent dynamical structural characteristics of DNA.
  Biophysical Journal 01/2006; 89(6):3721-40. · 3.65 Impact Factor
• Article: Molecular dynamics simulations of the 136 unique tetranucleotide sequences of DNA oligonucleotides. I. Research design and results on d(CpG) steps.

  David L Beveridge, Gabriela Barreiro, K Suzie Byun, David A Case, Thomas E Cheatham, Surjit B Dixit, Emmanuel Giudice, Filip Lankas, Richard Lavery, John H Maddocks, Roman Osman, Eleanore Seibert, Heinz Sklenar, Gautier Stoll, Kelly M Thayer, Péter Varnai, Matthew A Young
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  ABSTRACT: We describe herein a computationally intensive project aimed at carrying out molecular dynamics (MD) simulations including water and counterions on B-DNA oligomers containing all 136 unique tetranucleotide base sequences. This initiative was undertaken by an international collaborative effort involving nine research groups, the "Ascona B-DNA Consortium" (ABC). Calculations were carried out on the 136 cases imbedded in 39 DNA oligomers with repeating tetranucleotide sequences, capped on both ends by GC pairs and each having a total length of 15 nucleotide pairs. All MD simulations were carried out using a well-defined protocol, the AMBER suite of programs, and the parm94 force field. Phase I of the ABC project involves a total of approximately 0.6 mus of simulation for systems containing approximately 24,000 atoms. The resulting trajectories involve 600,000 coordinate sets and represent approximately 400 gigabytes of data. In this article, the research design, details of the simulation protocol, informatics issues, and the organization of the results into a web-accessible database are described. Preliminary results from 15-ns MD trajectories are presented for the d(CpG) step in its 10 unique sequence contexts, and issues of stability and convergence, the extent of quasiergodic problems, and the possibility of long-lived conformational substates are discussed.
  Biophysical Journal 01/2005; 87(6):3799-813. · 3.65 Impact Factor
• Article: Molecular Dynamics Simulations of the 136 Unique Tetranucleotide Sequences of DNA Oligonucleotides. I. Research Design and Results on d(C pG) Steps

  David L. Beveridge, Gabriela Barreiro, K. Suzie Byun, David A. Case, Thomas E. Cheatham, Surjit B. Dixit, Emmanuel Giudice, Filip Lankas, Richard Lavery, John H. Maddocks, Roman Osman, Eleanore Seibert
  [show abstract] [hide abstract]
  ABSTRACT: We describe herein a computationally intensive project aimed at carrying out molecular dynamics (MD) simulations including water and counterions on B-DNA oligomers containing all 136 unique tetranucleotide base sequences. This initiative was undertaken by an international collaborative effort involving nine research groups, the “Ascona B-DNA Consortium” (ABC). Calculations were carried out on the 136 cases imbedded in 39 DNA oligomers with repeating tetranucleotide sequences, capped on both ends by GC pairs and each having a total length of 15 nucleotide pairs. All MD simulations were carried out using a well-defined protocol, the AMBER suite of programs, and the parm94 force field. Phase I of the ABC project involves a total of ∼0.6μs of simulation for systems containing ∼24,000 atoms. The resulting trajectories involve 600,000 coordinate sets and represent ∼400 gigabytes of data. In this article, the research design, details of the simulation protocol, informatics issues, and the organization of the results into a web-accessible database are described. Preliminary results from 15-ns MD trajectories are presented for the d(CpG) step in its 10 unique sequence contexts, and issues of stability and convergence, the extent of quasiergodic problems, and the possibility of long-lived conformational substates are discussed.
  Biophysical Journal - BIOPHYS J. 01/2004; 87(6):3799-3813.
• Source

  Available from: hamilton.edu

  Article: Nucleic acid base pair dynamics: the impact of sequence and structure using free-energy calculations.

  Emmanuel Giudice, Richard Lavery
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  ABSTRACT: Molecular dynamics free-energy calculations of base pair opening within double helical DNA and RNA are used to explain why A-tracts (oligo-adenine repeats) greatly increase the lifetimes of AT base pairs, whereas the structural and the chemical changes involved in passing from B-DNA to A-RNA have comparatively small effects.
  Journal of the American Chemical Society 05/2003; 125(17):4998-9. · 9.91 Impact Factor
• Article: Base pair opening within B-DNA: free energy pathways for GC and AT pairs from umbrella sampling simulations.

  Emmanuel Giudice, Péter Várnai, Richard Lavery
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  ABSTRACT: The conformational pathways and the free energy variations for base opening into the major and minor grooves of a B-DNA duplex are studied using umbrella sampling molecular dynamics simulations. We compare both GC and AT base pair opening within a double-stranded d(GAGAGAGAGAGAG)* d(CTCTCTCTCTCTC) oligomer, and we are also able to study the impact of opening on the conformational and dynamic properties of DNA and on the surrounding solvent. The results indicate a two-stage opening process with an initial coupling of the movements of the bases within the perturbed base pair. Major and minor groove pathways are energetically comparable in the case of the pyrimidine bases, but the major groove pathway is favored for the larger purine bases. Base opening is coupled to changes in specific backbone dihedrals and certain helical distortions, including untwisting and bending, although all these effects are dependent on the particular base involved. Partial opening also leads to well defined water bridging sites, which may play a role in stabilizing the perturbed base pairs.
  Nucleic Acids Research 04/2003; 31(5):1434-43. · 8.03 Impact Factor
• Article: Simulations of nucleic acids and their complexes.

  Emmanuel Giudice, Richard Lavery
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  ABSTRACT: Recent years have seen considerable progress in simulations of nucleic acids. Improvements in force fields, simulation techniques and protocols, and increasing computer power have all contributed to making nanosecond-scale simulations of both DNA and RNA commonplace. The results are already helping to explain how nucleic acids respond to their environment and to their base sequence and to reveal the factors underlying recognition processes by probing biologically important nucleic acid-protein interactions and medically important nucleic acid-drug complexation. This Account summarizes methodological progress and applications of molecular dynamics to nucleic acids over the past few years and tries to identify remaining challenges.
  Accounts of Chemical Research 07/2002; 35(6):350-7. · 21.64 Impact Factor
• Article: Analysis of peptide rotational diffusion by homonuclear NMR.

  Thérèse E Malliavin, Emmanuel Giudice
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  ABSTRACT: The analysis of the rotational diffusion of a molecule using homonuclear NMR is investigated. The homonuclear longitudinal and transverse cross-relaxation rates, which can be quantitatively measured using off-Resonance Rotating frame nuclear Overhauser Effect Spectroscopy (ROESY), are used to build a distribution, which exhibits a solid-state-like pattern characteristic of the diffusion tensor. The distributions of the antimicrobial peptide ranalexin in water and in 30% of trifluoracetic acid (TFE) are compared, and the peptide rotational diffusion is shown to be more isotropic in water than in 30% TFE. This difference is further supported by the analysis of NMR ranalexin conformers in 30% TFE, and by the analysis of a molecular dynamics simulation of peptide in water.
  Biopolymers 05/2002; 63(5):335-42. · 2.87 Impact Factor
• Article: Energetic and Conformational Aspects of A:T Base-Pair Opening within the DNA Double Helix.

  Emmanuel Giudice, Péter Várnai, Richard Lavery
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  ABSTRACT: Free energy profiles of opening of a centrally placed A:T pair within a DNA oligomer exhibits two regimes: Elastic deformation due to hydrogen bond rupture and a roughly linear region due to loss of stacking and solvation. Thymine opens equally easily into the minor and major grooves, while adenine favors the major groove direction. No significant variations from canonical backbone conformations were observed; however base opening induces considerable changes in surrounding solvent distribution, leading finally to a water channel which passes through the double helix.
  ChemPhysChem 11/2001; 2(11):673-677. · 3.41 Impact Factor
• Article: Molecular Dynamics Simulations of the 136 Unique Tetranucleotide Sequences of DNA Oligonucleotides. I. Research Design and Results on $d\left(C{}_{p}G \right)$ Steps

  David L Beveridge, Gabriela Barreiro, K Suzie Byun, David A Case, Thomas E. Cheatham III, Surjit B Dixit, Emmanuel Giudice, Filip Lankas, Richard Lavery, John H Maddocks, Roman Osman, Eleanore Seibert, Heinz Sklenar, Gautier Stoll, Kelly M Thayer, Péter Varnai, Matthew A Young