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Dynamics of Substrate Binding to Copper Zinc Superoxide Dismutase
Stuart A. Allison and J. Andrew McCammon
The association dynamics of the substrate superoxide and the enzyme superoxide dismutase have been studied by computer simulation of the relative diffusion of these reaction partners. Electrostatic interactions are found to bias the substrate trajectories toward the active site of the enzyme, leading to a significant enhancement of the reaction rate.
Atomic Motions in Phenylalanine Transfer RNA Probed by Molecular Dynamics Simulations
M. Prabhakaran, J.A. McCammon and S.C. Harvey
Molecular-Dynamics Simulation of Phenylalanine Transfer RNA. I. Methods and General Results
Stephen C. Harvey, M. Prabhakaran and J. Andrew McCammon
A 24-ps molecular-dynamics simulation of motions in yeast tRNAPhe has been completed. The overall structure of the molecule is well preserved, for the motions represent fluctuations about an average structure that is very much like the crystallographic structure. The four helical stems remain intact, the structures of the loop regions do not deteriorate, and even the base stacking in the single-stranded amino acid acceptor terminus is maintained. With two exceptions, none of the sugar puckers is significantly changed. The unconstrained floppy motions of base A76 are responsible for the repuckering of ribose 76. The other sugar that repuckers is ribose, 46, and this is the result of a very small structural change in the center of the molecule that is also responsible for the breakage of one tertiary hydrogen bond. This change in local structure does not seriously distort the base-stacking and intercalation patterns where the variable loop and the D-stem interact.
Molecular-Dynamics Simulation of Phenylalanine Transfer RNA. II. Amplitudes, Anisotropies and Anharmonicities of Atomic Motions
M. Prabhakaran, Stephen C. Harvey and J. Andrew McCammon
The atomic motions from a molecular-dynamics simulation of yeast tRNAPhe are analyzed and compared with those observed in protein simulations. In general, the tRNA motions are of larger amplitude, they are more anisotropic, and they arise from potentials of mean force that are more anharmonic than in the protein case. In both cases, the amplitudes are largest for atoms on the surface of the molecules. On the other hand, the most anisotropic and anharmonic atomic motions are generally found in the interior of the tRNA, while they are found on the surface of the protein. These differences are discussed in terms of the differences in structure between nucleic acids and proteins.
Brownian Dynamics with Rotation-Translation Coupling
Eric Dickinson, Stuart A. Allison and J. Andrew McCammon
A generalized algorithm is proposed for simulating a system of interacting spherical particles simultaneously executing both rotational and translational Brownian motion. Rotation-translation couplings are obtained numerically for (a) a pair of rigid spheres using the generalized algorithm and (b) a pair of rigid cubic octamer particles using a translational algorithm with rigid constraints. The likely importance of rotation-translation coupling in the Brownian-dynamics context is discussed.
Simulation of the Diffusion-Controlled Reaction Between Superoxide and Superoxide Dismutase. I. Simple Models
S.A. Allison, G. Ganti and J.A. McCammon
A Brownian dynamics simulation method is used to study the diffusion-influenced bimolecular reaction between superoxide and superoxide dismutase (SOD). Using simple models, the details of which are based on the crystallographic structure of SOD, it is found that the electrostatic charge distribution of SOD serves to guide superoxide into the active site and enhance the diffusion-controlled rate constant by about 40%.
Molecular Dynamics with Stochastic Boundary Conditions
Simulation of Activated Processes
Simulation of Diffusional Encounters
Theoretical Molecular Biology: Some Recent Developments
J.A. McCammon, S.A. Allison and S.H. Northrup
Journal of Molecular Science (China), Vol. 3, pp. 193-204 (1985, Invited review)
Brownian Dynamics of Diffusion-Controlled Reactions: The Lattice Method
G. Ganti, J.A. McCammon and S.A. Allison
An extended version of the Brownian dynamics trajectory approach for calculating rate constants of bimolecular diffusion-controlled reactions is introduced. The extended approach allows detailed study of systems with many interaction centers by avoiding the need to recompute the intermolecular force between the reactants at each step of each trajectory. Instead, the net force is interpolated from reference values corresponding to points on a lattice that covers the diffusion space. As an illustration, the method is applied to study the diffusion-controlled reaction of the substrate superoxide with the enzyme superoxide dismutase, where the latter has as many as 2196 electrostatic charges influencing the substrate motion.
Dynamics of Proteins: Elements and Function
M. Karplus and J.A. McCammon
Extended Brownian Dynamics of Diffusion Controlled Reactions
S.A. Allison, S.H. Northrup and J.A. McCammon
The Brownian dynamics simulation method of Northrup et al. is extended so that dynamical trajectories can be initiated with the reactants in close proximity to one another. A more general analysis is presented which shows that this procedure is exact in cases where the first-time encounter flux to the more proximal starting surface is isotropic, such as cases where interparticle forces are centrosymmetric, but is approximate otherwise. Diffusion controlled rate constants for three model systems obtained by this procedure are compared with analytic results or with exact rate constants derived from simulations following the original Northrup procedure. Agreement is good to excellent in all cases considered. The extended method is expected to be of considerable practical importance in systems with highly anisotropic reactivity where it is computationally inefficient to obtain rate constants by the original method.
Computer Graphics and Moving Pictures in the Analysis of Intramolecular Motions in Phenylalanine Transfer RNA
S.C. Harvey, M. Prabhakaran, F.L. Suddath and J.A. McCammon
Hydration of Chloride and Bromide Anions: Determination of Relative Free Energy by Computer Simulation
Terry P. Lybrand, Indira Ghosh and J. Andrew McCammon
Computer-simulation techniques that can reliably predict relative free energies of reactions have great potential usefulness in chemistry, biochemistry, and pharmacology. Such techniques could be used to calculate relative solubilities, relative free energies of binding for ligand-receptor complexes, and relative free energies of activation (Le., relative reaction rates). In particular, the ability to calculate relative free energies of solvation is of special interest. For example, relative free energies of solvation (or more precisely, relative free energies of desolvation) often play a major role in determining the relative binding affinity of two ligands at a common receptor site.