Showing papers by "Thomas E. Cheatham published in 2000"

Calculating Structures and Free Energies of Complex Molecules: Combining Molecular Mechanics and Continuum Models

Abstract: A historical perspective on the application of molecular dynamics (MD) to biological macromolecules is presented. Recent developments combining state-of-the-art force fields with continuum solvation calculations have allowed us to reach the fourth era of MD applications in which one can often derive both accurate structure and accurate relative free energies from molecular dynamics trajectories. We illustrate such applications on nucleic acid duplexes, RNA hairpins, protein folding trajectories, and protein−ligand, protein−protein, and protein−nucleic acid interactions.

Molecular dynamics simulation of nucleic acids: successes, limitations, and promise.

Abstract: In the last five years we have witnessed a significant increase in the number publications describing accurate and reliable all-atom molecular dynamics simulations of nucleic acids. This increase has been facilitated by the development of fast and efficient methods for treating the long-range electrostatic interactions, the availability of faster parallel computers, and the development of well-validated empirical molecular mechanical force fields. With these technologies, it has been demonstrated that simulation is not only capable of consistently reproducing experimental observations of sequence specific fine structure of DNA, but also can give detailed insight into prevalent problems in nucleic acid structure, ion association and specific hydration of nucleic acids, polyadenine tract bending, and the subtle environmental dependence of the A-DNA-B-DNA duplex equilibrium. Despite the advances, there are still issues with the methods that need to be resolved through rigorous controlled testing. In general, these relate to deficiencies of the underlying molecular mechanical potentials or applied methods (such as the imposition of true periodicity in Ewald simulations and the need for energy conservation), and significant limits in effective conformational sampling. In this perspective, we provide an overview of our experiences, provide some cautionary notes, and provide recommendations for further study in molecular dynamics simulation of nucleic acids.

Molecular dynamics simulation of nucleic acids.

Abstract: We review molecular dynamics simulations of nucleic acids, including those completed from 1995 to 2000, with a focus on the applications and results rather than the methods. After the introduction, which discusses recent advances in the simulation of nucleic acids in solution, we describe force fields for nucleic acids and then provide a detailed summary of the published literature. We emphasize simulations of small nucleic acids (∼6 to 24 mer) in explicit solvent with counterions, using reliable force fields and modern simulation protocols that properly represent the long-range electrostatic interactions. We also provide some limited discussion of simulation in the absence of explicit solvent. Absent from this discussion are results from simulations of protein-nucleic acid complexes and modified DNA analogs. Highlights from the molecular dynamics simulation are the spontaneous observation of A B transitions in duplex DNA in response to the environment, specific ion binding and hydration, and reliable rep...