Molecular Dynamics Systems AMBER

In a QM/MM calculation [31,32], the system is partitioned into two regions a QM region, typically consisting of a relatively small number of atoms relevant for the specific process being studied, and a MM region with all the remaining atoms. This scheme has been recently implemented in the Amber Molecular Dynamics package with support for various semi-empirical Hamiltonians [33,34], The total Hamiltonian (H) for such a system is written as... 

There are several MM force fields available, such as OPLS [29], CHARMM [30], AMBER [31], GROMOS [32], MMFF [33], CVFF [34], to mention a few. Several of them have been combined with the QM calculation programs and used in the combined QM/MM molecular dynamics simulations. [12,15,35,36] In our own work we have combined either GAUSSIAN94 [24] or GAMESS [25] with our own simulation software which is the modified version of McMOLDYN [37] package to study solvation phenomena and radical systems [38,39]. 

Kollman and coworkers apphed a variety of computational methods to this mechanistic problem—including quantum mechanics on small model systems, molecular dynamics simulations with the AMBER force field on the whole ODCase-substrate system, and MM-PBSA free energy calculations on ODCase with bound OMP [38]. Based on their results, they proposed a decarboxylation mechanism for ODCase that involves C5 protonation. Their calculations at the MP2/6-31+G //HF/6-31+G level showed that C5 has a greater intrinsic proton affinity than C6, 02, and even 04. This, coupled with the fact that Lys72 (M. thermoautotrophicum numbering see Table 2) is near C5 and C6 in the inhibitor-bound crystal structures, prompted the authors to embrace a C5 protonation mechanism. However, the authors themselves acknowledged the uncertainties of their calculations because of approximations employed in representing the enzyme active site. 

Relative pK calculations are the main method used to determine pK shifts in biomolecular systems. Such calculations have error bars of several pK units for the determination of the pK values for amino acid side chains on a protein [155-157], Because biomolecular systems such as proteins are very large, molecular dynamics simulations use empirical potentials such as AMBER, CHARMM, and OPLS [52], Correspondingly, solvation models are fitted [158] for use with empirical potentials, such as Sharma and Kaminski s fuzzy-border continuum model [159],... 

Lennard-Jones potentials. Because it is not our intention to review all advantages and applications of these different functional forms and parameter sets, we shall focus our explanations to the well-known AMBER force field (2, 3). This parameter set is widely used, and has already been successfully applied to molecular dynamics simulations of various surfactant systems. 

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