Force field results AMBER

MD simulations on DNA oligonucleotides including water explicitly were first reported by Seibel et ah Subsequent calculations in this view on B forms of DNA were reported by van Gunsteren et al." and Zielinski and Shibata" and on Z-DNA by Laaksonen. Fritsch et al." reported MD simulations on poly(dA) poly(dT) based on the Weiner et al. force field in AMBER 3.0, comparing implicit and explicit models for including solvent. The results were consistent with B form DNA, with a tendency in the hydrated form to adopt a slightly distorted, unwound, and relatively stretched conformation. The results were examined with respect to the idea of three-center, interbase pair hydrogen bonds. A possibility of these forms was indicated, but the mean lifetimes were found to be short. 

Assisted model building with energy refinement (AMBER) is the name of both a force field and a molecular mechanics program. It was parameterized specifically for proteins and nucleic acids. AMBER uses only five bonding and nonbonding terms along with a sophisticated electrostatic treatment. No cross terms are included. Results are very good for proteins and nucleic acids, but can be somewhat erratic for other systems. 

University of California, San Francisco. The original AMBER has become one of the more widely used academic force fields and extensive work has gone into developing it — resulting in a number of versions of the method and associated parameters. Hyper-Chem gives results equivalent to Versions 2.0 and 3.0a of the AMBERprogram distributed by the Kollman group and parameter sets for both these versions are distributed with HyperChem. 

In the ONIOM(QM MM) scheme as described in Section 2.2, the protein is divided into two subsystems. The QM region (or model system ) contains the active-site selection and is treated by quantum mechanics (here most commonly the density functional B3LYP [31-34]). The MM region (referred to as the real system ) is treated with an empirical force field (here most commonly Amber 96 [35]). The real system contains the surrounding protein (or selected parts of it) and some solvent molecules. To analyze the effects of the protein on the catalytic reactions, we have in general compared the results from ONIOM QM MM models with active-site QM-only calculations. Such comparisons make it possible to isolate catalytic effects originating from e.g. the metal center itself from effects of the surrounding protein matrix. 

MD simulations provide a detailed insight in the behavior of molecular systems in both space and time, with ranges of up to nanometers and nanoseconds attainable for a system of the size of a CYP enzyme in solution. However, MD simulations are based on empirical molecular mechanics (MM) force field descriptions of interactions in the system, and therefore depend directly on the quality of the force field parameters (92). Commonly used MD programs for CYPs are AMBER (93), CHARMM (94), GROMOS (95), and GROMACS (96), and results seem to be comparable between methods (also listed in Table 2). For validation, direct comparisons between measured parameters and parameters calculated from MD simulations are possible, e.g., for fluorescence (97) and NMR (cross-relaxation) (98,99). In many applications where previously only energy minimization would be applied, it is now common to perform one or several MD simulations, as Ludemann et al. and Winn et al. (100-102) performed in studies of substrate entrance and product exit. 

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