Publications. (Want annotations?)

N. Spackova, T. E. Cheatham, III, F. Ryjacek, F. Lankas, L. van Meervelt, P. Hobza, and J. Sponer. ''Molecular dynamics simulations and thermodynamics analysis of DNA-drug complexes. Minor groove binding between 4.-6-diamino-2-phenylindole and DNA duplexes in solution''. J. Amer. Chem. Soc. 125, 1759-1769 (2003).
     [ local PDF: PubMed: JACS: WOS ]

An extensive set of simulations investigates the binding of DAPI to the minor groove of DNA in multiple possible binding modes. Analysis includes investigation of the hydration, dynamics and estimation of the binding affinity. The results suggest that inclusion of a small amount of water can improve the MM_PBSA results.

R. Stefl, T. E. Cheatham, III, N. Spackova, E. Fadrna, I. Berger, J. Koca, and J. Sponer. ``Formation pathways of a guanine-quadruplex DNA revealed by molecular dynamics and thermodynamical analysis of the substates''. Biophys. J. 85, 1787-1804 (2003).
     [ local PDF: PubMed: Biophys J: WOS ]

A large set of simulations of DNA quadruplexes and various possible models on the folding pathway investigate the formation of quadruplex DNA. Dimer and trimer models converge into distinct structures. Free energy analysis highlights the importance of including bound ions.

J. P. Lewis, T. E. Cheatham, III, H. Wang, E. Starikow, and O. F. Sankey. ``Dynamically amorphous character of electronic states in poly(dA)-poly(dT) DNA''. J. Phys. Chem. B 107, 2581-2587 (2003).
     [ local PDF: JPC B: WOS ]

DFT post-processing of DNA duplex configurations sampled from atomistic MD simulation in explicit solvent highlight the electronic states and dependence on the thermal motion of the DNA.

F. Lankas, J. Sponer, J. Langowski & T. E. Cheatham, III. ``DNA base-pair step deformability inferred from molecular dynamics simulation''. Biophys. J. 85, 2872-2883 (2003)
     [ local PDF: PubMed: Biophys J ]

In comparison with crystal experiment, MD simulation gives insight into the elasticity of DNA base pair steps.

F. Lankas, T. E. Cheatham, III, P. Hobza, J. Langowski, N. Spackova, and J. Sponer. ``Critical effect of the N2 amino group on structure, dynamics and elasticity of DNA polypurine tracts''. Biophys. J. 82, 2592-2609 (2002).
     [ local PDF: PubMed: Biophys J: WOS ]

The elasticity of overall DNA duplexes is compared for various sequences.

J. P. Lewis, J. Pikus, T. E. Cheatham, III, E. B. Starikov, H. Wang, J. Tomfohr, and O. F. Sankey. ``A comparison of electronic states in periodic and aperiodic poly(dA)-poly(dT) DNA''. Phys. Stat. Sol. (b) 233, 90-100 (2002).
     [ local PDF: Wiley: WOS ]

T. E. Cheatham, III and M. A. Young. ``Molecular dynamics simulations of nucleic acids: Successes, limitations and promise''. Biopolyers Nuc. Acid Sci. 56, 232-256 (2001).
     [ local PDF: PubMed: Biopolymers: WOS ]

Although this work provides a fair bit of review, it also contains new material discussing minimal solvent models, comparison's of DNA force fields, and lack of ion distribution convergence in 10 ns length simulation.

T. E. Cheatham, III, B. R. Brooks & P. A. Kollman. ``Molecular modeling of nucleic acid structure: Energy and sampling'' in Current Protocols in Nucleic Acid Chemistry. (Wiley: New York) 7.8.1-7.8.21 (2001)

T. E. Cheatham, III, B. R. Brooks & P. A. Kollman. ``Molecular modeling of nucleic acid structure: Electrostatics and solvation'' in Current Protocols in Nucleic Acid Chemistry. (Wiley: New York) 7.9.1-7.9.22 (2001).

T. E. Cheatham, III, B. R. Brooks & P. A. Kollman. ``Molecular modeling of nucleic acid structure: Setup and analysis'' in Current Protocols in Nucleic Acid Chemistry. (Wiley: New York) 7.10.1-7.10.18 (2001).

T. E. Cheatham, III & P. A. Kollman. ``Molecular dynamics simulations of nucleic acids'' in Ann. Rev. Phys. Chem. 51, 434-471 (2000).
     [ local PDF: PubMed: Ann Rev Phys Chem: WOS ]

A fairly comprehensive review of molecular dynamics simulation of small nucleic acids in solution from the ~1995-2000 time frame with a particular focus on DNA. Absent from this discussion is results from simulations of protein-nucleic acid complexes and modified DNA analogues (since the reviewers/editors said it was too long!). Highlights from the molecular dynamics simulations are the spontaneous observation of A<->B transitions in duplex DNA in response to the environment, specific ion binding and hydration, and reliable representation of nucleic acid bending.

T. E. Cheatham, III, B. R. Brooks & P. A. Kollman. ``Molecular modeling of nucleic acid structure'' in Current Protocols in Nucleic Acid Chemistry1: 7.5.1-7.5.12. Wiley: New York (2000).

P. A. Kollman, I. Massova, C. Reyes, B. Kuhn, S. Huo, L. Chong, M. Lee, T. Lee, Y. Duan, W. Wang, O. Donini, P. Cieplak, J. Srinivasan, D. A. Case & T. E. Cheatham, III. ``Calculating structures and free energies of complex molecules: Combining molecular mechanics and continuum models.'' Acc. Chem. Res. 33, 889-897 (2000).
     [ local PDF: PubMed: Acc Chem Res: WOS ]

This is the first unit in a series to appear in Current Protocols discussing molecular modeling and molecular simulation of nucleic acid systems. This first unit, targeted at an introductory level, introduces molecular modeling of nucleic acids and discusses issues in model building. Subsequent units delve into the details of realistic simulation of nucleic acids in solution, discussing molecular simulation methods (MD, Monte Carlo, minimization), force fields, solvation, electrostatics and other important issues.

T. E. Cheatham, P. Cieplak & P. A. Kollman. ``A modified version of the Cornell et al. force field with improved sugar pucker phases and helical repeat.'' J. Biomol. Struct. Dyn. 16, 845-862 (1999).
     [ PubMed: WOS ]

Extensive simulations were performed, applying higher levels of ab initio theory on entire nucleosides and extensive molecular dynamics simulation of various nucleic acid duplexes in solution in an attempt to alter the torsional potential of the Cornell et al. force field to fix up known difficiencies. This includes improving the sugar pucker phases and increasing the helical twist. This modified force field (available from ftp://par10.mgsl.dcrt.nih.gov:/pub/parm98.dat) leads to better B-DNA and A-RNA, with more realistic sugar puckers and helical repeat, however some environmental dependence in the force field is lost (i.e. spontaneous B->A transitions with Co(NH3)6 3+ ions or stabilization of A-DNA in mixed water/ethanol is no longer seen!)

D. E. Konerding, T. E. Cheatham, III, P. A. Kollman & T. L. James. ``Restrained molecular dynamics of solvated duplex DNA using the particle mesh Ewald method'' J. Biomol. NMR. 13, 119-131 (1999).
[ local PDF: PubMed: J Biomol NMR ]

What happens when we include solvent and a proper treatment of the long ranged electrostatic interactions in NMR refinement? The structure appears more ``realistic'', however there is statistically no better fit to the NMR data...

J. L. Miller, T. E. Cheatham, III, & P. A. Kollman. "Simulation of Nucleic Acid Structure." Oxford Handbook of Nucleic Acid Structure S. Neidle, editor; Oxford University Press, pp. 95-115 (1999).

A review of simulation methods applied to nucleic acids.

M. F. Crowley, T. A. Darden, T. E. Cheatham, III & D. Deerfield. "Fine- and coarse-grain parallel AMBER and particle mesh Ewald on MPP's" in Parallel Computing for Industrial and Scientific Applications, Eds: J. Jenness (Morgan-Kaufmann) (1999).

T. E. Cheatham, III & B. R. Brooks. ``Recent advances in molecular dynamics simulation towards realistic representation of biomolecules in solution". Theor. Chem. Acc. 99, 279-288 (1998).
     [ local PDF: SpringerLink: WOS ]

A review of MD applied to biomolecular systems highlighting issues in the simulations including proper representation of the long range electrostatics, periodicity vs. cutoff effects, including solvent and other subtle issues of the methods.

T. E. Cheatham, J. Srinivasan, D. A. Case & P. A. Kollman. ``Molecular dynamics and continuum solvent studies of the stability of polyG-polyC and polyA-polyT DNA duplexes in solution.'' J. Biomol. Struct. Dyn. 16, 265-280 (1998).

     [ PubMed: WOS ]

Post-processing the trajectories, estimating the solute energy in the gas phase, an estimate of the solute entropy and solvation added back in through continuum theory can give useful insight into the relative energetics of different molecular systems, for example the comparison of A-DNA vs. B-DNA in polyG-polyC and polyA-polyT duplexes. This is an extension of the analysis by Srinivasan et al. (see below) and shows that polyG sequences are more A-phillic.

T. E. Cheatham, III & P. A. Kollman. ``Molecular dynamics simulation of nucleic acids in solution: How sensitive are the results to small perturbations in the force field and environment?'' in Structure, Motion, Interactions and Expression of Biological Macromolecules, Proceedings of the 10th Conversation. Eds: R.H. Sarma & M.H. Sarma (Adenine Press) p. 99-116 (1998).

Surprisingly, the structure of a nucleic acid duplex with the Cornell et al. force field is not that sensitive to small perturbations in the environment on a 1 nanosecond time scale, such as different water models, reduced stacking interactions, etc. The structure is however very sensitive to the sugar pucker.

T. E. Cheatham, III, J. L. Miller, T. I. Spector, P. Cieplak & P. A. Kollman. ``Molecular dynamics simulations on nucleic acid systems using the Cornell et al. force field and particle mesh Ewald electrostatics.'' in Modeling and Structure Determination of Nucleic Acids. Eds: N.B. Leontis & J. Santa Lucia Jr (ACS: Washington, DC) p. 285-303 (1998).

A review of the work in the Kollman group on nucleic acid systems up until the early 1998 time frame.

S. Bogusz, T. E. Cheatham, III & B. R. Brooks. ``Removal of pressure and free energy artifacts in charged periodic systems via net charged corrections to the Ewald potential.'' J. Chem. Phys. 108, 7070-7084 (1998).
     [ WOS ]

The goal of this work is to investigate the application of Ewald methods in free energy studies when the net-charge on the system changes. Of particular interest is removing energy and pressure artifacts.

J. Srinivasan, T. E. Cheatham, III, P. Cieplak, P. A. Kollman & D. A. Case. ``Continuum solvent studies of the stability of DNA, RNA and phosphoramidate-DNA helices.'' J. Amer. Chem. Soc. 120, 9401-9409 (1998).
     [ local PDF: JACS: WOS ]

Using our previously generated trajectories, estimates of the relative free energy difference between (meta)stable simulations have been obtained. The results suggest that B-RNA is in fact less stable than A-RNA with the Cornell et al. force field, and therefore the reason why B-RNA is stable is that the barrier between A-RNA and B-RNA can not be surmounted in nanosecond length simulations.

S. C. Harvey, R. K.-Z. Tan & T. E. Cheatham, III. ``The flying ice cube: Velocity rescaling in molecular dynamics leads to violation of energy equipartition.'' J. Comp. Chem.19, 726-740 (1998).
     [ local PDF: JCC: WOS ]

If rigorous energy conservation is not maintained and simple scaling of the velocities is performed to control temperature, kinetic energy nncan accumulate in low frequency modes...

P. A. Kollman, D. A. Pearlman, D. A. Case, J. W. Caldwell, W. S. Ross, T. E. Cheatham, III, S. DeBolt, D. M. Ferguson & G . Seibel. ``AMBER'' in Encyclopedia of Computational Chemistry Wiley-Interscience:NY (1998).

M. Hodoscek, E. M. Billings, T. E. Cheatham, III & B. R. Brooks. ``High performance computing in biophysics: Recent experiences and developments of CHARMM.'' Proceedings of the International Symposium on Supercomputing: New Horizons of Computational Science. Kluwer Academic (1998).

T.E. Cheatham, III & P.A. Kollman. ``Insight into the stabilization of A-DNA by specific ion association: Spontaneous B-DNA to A-DNA transitions observed in molecular dynamics simulations of d[ACCCGCGGGT]2 in the presence of hexaamminecobalt(III).'' Structure 5, 1297-1311 (1997).
     [ local PDF: PubMed: Structure: WOS ]

Simulations of d[ACCCGCGGGT]2 with and without specifically bound hexaamminecobalt(III) are presented. When 2 hexaamminecobalt(III) ions are bound to the GGG stretches in the major groove and 2 other of these ions are loosely associated with the backbone (likely bridging the bend across the major groove that leads to close approach of the phosphate groups) A-DNA is stabilized and spontaneous B-DNA to A-DNA transitions are observed. This gives further evidence that hydration and ion association in the major groove of DNA stabilize the A-DNA conformation.

T.E. Cheatham, III, M.F. Crowley, T. Fox & P.A. Kollman. ``A molecular level picture of the stabilization of A-DNA in mixed ethanol-water solutions'' Proc. Natl. Acad. Sci. 94, 9626-9630 (1997).
     [ local PDF: PubMed: PNAS: PubMed Central ]

Simulations on d[CCAACGTTGG]2 in pure ethanol and ~85% ethanol are presented. In pure ethanol, the structures move away from canonical A-DNA and B-DNA and the structure is characterized by local structural distortions. In ~85% ethanol, A-DNA is stabilized over 3 nanosecond PME simulations with the Cornell et al. force field. B-DNA is also stable in 85% ethanol, unless a small modification to the V2 term on the OCCO torsions dropping the force constant from 1.0 to 0.3 kcal/mol is applied which leads to spontaneous B-DNA to A-DNA transition at 1.5 ns.

T.E. Cheatham, III & P. A. Kollman. ``Molecular dynamics simulations highlight the structural differences among DNA:DNA, RNA:RNA and DNA:RNA hybrid duplexes'' J. Amer. Chem. Soc. (1997) 119 4805-4825.
     [ local PDF: JACS: WOS ]

Simulations on DNA, RNA and hybrid duplexes of the d[CCAACGTTGG]2 sequence applying the particle mesh Ewald method and Cornell et al force field on canonical A and canonical B models. Emphasis in the analysis is on the flexibility and hydration.

P. Cieplak, T.E. Cheatham, III & P.A. Kollman. ``Molecular dynamics simulations find that 3' phosphoramidate modified DNA duplexes undergo a B to A transition and normal DNA duplexes an A to B transition.'' J. Amer. Chem. Soc. 119, 6722-6730 (1997).
     [ local PDF: JACS: WOS ]

T. Spector, T. E. Cheatham, III & P.A. Kollman. ``Unrestrained molecular dynamics of photodamaged DNA in aqueous solution.'' J. Amer. Chem. Soc. 119, 7095-7104 (1997).
     [ local PDF: JACS: WOS ]

M. F. Crowley, T. A. Darden, T. E. Cheatham, III & D. Deerfield. ``Adventures in improving the scaling and accuracy of a parallel molecular dynamics program.'' J. Supercomputing 11(3), 255-278 (1997).
     [ WOS ]

T. A. Darden, L. G. Pedersen, A. Y. Toukmaji, M. F. Crowley & T. E. Cheatham, III. ``Particle-mesh based methods for fast Ewald summation in molecular dynamics simulations''. Proceedings of the Eighth SIAM Conference on Parallel Processing for Scientific Computing. M. Heath et al., editors. Minn, MN. March (1997).

T. E. Cheatham, III, J. L. Miller, T. I. Spector, P. Cieplak & P. A. Kollman. ``Molecular dynamics simulations on nucleic acid systems using the Cornell et al. force field and particle mesh Ewald electrostatics.'' in Modeling and Structure Determination of Nucleic Acids, ACS Symposium Series No. 682. Leontis, NB & Santa Lucia, Jr J, editors. p 285-303 (1997).

T.E. Cheatham, III & P.A. Kollman. ``Observation of the A DNA to B DNA transition during unrestrained molecular dynamics in aqueous solution.'' J. Mol. Biol. 259:(3), 434-444 (1996).
     [ local PDF: PubMed: DOI ]

A paper discussing the results of 4 nanosecond length molecular dynamics run (with the particle mesh Ewald method and Cornell et al. force field) on d[CCAACGTTGG]2, two started in a canonical A form and two started in a canonical B form. All converge to a common "B family" structure...

T.E. Cheatham, III, J.L. Miller, T. Fox, T.A. Darden and P.A. Kollman. ``Molecular dynamics simulations on solvated biomolecular systems: The Particle Mesh Ewald method leads to stable trajectories of DNA, RNA, and proteins.'' J. Amer. Chem. Soc. 117, 4193 (1995).
[ JACS ]

D.A. Pearlman, D.A. Case, J.W. Caldwell, W.S. Ross, T.E. Cheatham III, S. DeBolt, D.M. Ferguson, G.L. Seibel and P.A. Kollman. ``AMBER, a package of computer programs for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to simulate the structural and energetic properties of molecules.'' Computer Physics Communications, 91, 1-41. (1995)

The first real code description paper of AMBER since AMBER 1.0. It talks about the various programs and algorithms implemented in AMBER.