Simulated annealing dynamics

Several molecular dynamics simulation approaches are available, including regular simulation, constrained simulation, and simulated annealing techniques. In addition, the simulated annealing dynamics simulation also was popular in computational chemistry studies of proteins and drug molecules (34.44.45). A common experimental protocol has been widely used in molecular dynamics simulation as following (34.46.47) ... 

D. D. Humphreys, R. A. Friesner, and B. J. Berne. Simulated annealing of a protein in a continuum solvent by multiple-time-step molecular dynamics. J. Phys. Chem., 99 10674-10685, 1995. 

Other methods which are applied to conformational analysis and to generating multiple conformations and which can be regarded as random or stochastic techniques, since they explore the conformational space in a non-deterministic fashion, arc genetic algorithms (GA) [137, 1381 simulation methods, such as molecular dynamics (MD) and Monte Carlo (MC) simulations 1139], as well as simulated annealing [140], All of those approaches and their application to generate ensembles of conformations arc discussed in Chapter II, Section 7.2 in the Handbook. 

Quenched dynamics is a combination of high temperature molecular dynamics and energy minimization. This process determines the energy distribution of con formational families produced during molecular dynamics trajectories. To provide a better estimate of conformations, you should combine quenched dynamics with simulated annealing. 

Otieriched dynam ics can trap structures in local minima. I o prevent this problem, you can cool the system slowly to room temperature or some appropriate lower temperature. I heu run room letTiperature m olecti lar dyn am ics sim ulation s to search for con formations that have lower energies, closer to the starting structure. Cooling a structure slowly is called simulated annealing. 

Humphreys D D, R A Friesner and B ] Berne 1995. Simulated Annealing of a Protein in a Continuu Solvent by Multiple Time-step Molecular Dynamics. Journal of Physical Chemistry 99 10674-1068... 

Solving Protein Structures Using Restrained Molecular Dynamics and Simulated Annealing... 

A particularly important application of molecular dynamics, often in conjunction with the simulated annealing method, is in the refinement of X-ray and NMR data to determine the three-dimensional structures of large biological molecules such as proteins. The aim of such refinement is to determine the conformation (or conformations) that best explain the experimental data. A modified form of molecular dynamics called restrained moleculai dynarrdcs is usually used in which additional terms, called penalty functions, are added tc the potential energy function. These extra terms have the effect of penalising conformations... 

A key feature of the Car-Parrinello proposal was the use of molecular dynamics a simulated annealing to search for the values of the basis set coefficients that minimise I electronic energy. In this sense, their approach provides an alternative to the traditioi matrix diagonalisation methods. In the Car-Parrinello scheme, equations of motion ... 

Model optimization is a further refinement of the secondary and tertiary structure. At a minimum, a molecular mechanics energy minimization is done. Often, molecular dynamics or simulated annealing are used. These are frequently chosen to search the region of conformational space relatively close to the starting structure. For marginal cases, this step is very important and larger simulations should be run. 

The tests in the two previous paragraphs are often used because they are easy to perform. They are, however, limited due to their neglect of intermolecular interactions. Testing the effect of intennolecular interactions requires much more intensive simulations. These would be simulations of the bulk materials, which include many polymer strands and often periodic boundary conditions. Such a bulk system can then be simulated with molecular dynamics, Monte Carlo, or simulated annealing methods to examine the tendency to form crystalline phases. 

Modeling in NMR Structure Determination B. Molecular Dynamics Simulated Annealing... 

Figure 5 Optimization of the objective function in Modeller. Optimization of the objective function (curve) starts with a random or distorted model structure. The iteration number is indicated below each sample structure. The first approximately 2000 iterations coiTespond to the variable target function method [82] relying on the conjugate gradients technique. This approach first satisfies sequentially local restraints, then slowly introduces longer range restraints until the complete objective function IS optimized. In the remaining 4750 iterations, molecular dynamics with simulated annealing is used to refine the model [83]. CPU time needed to generate one model is about 2 mm for a 250 residue protein on a medium-sized workstation.

To overcome the limitations of the database search methods, conformational search methods were developed [95,96,109]. There are many such methods, exploiting different protein representations, objective function tenns, and optimization or enumeration algorithms. The search algorithms include the minimum perturbation method [97], molecular dynamics simulations [92,110,111], genetic algorithms [112], Monte Carlo and simulated annealing [113,114], multiple copy simultaneous search [115-117], self-consistent field optimization [118], and an enumeration based on the graph theory [119]. 

A Sail, TL Blundell. Definition of general topological equivalence m protein structures A procedure involving comparison of properties and relationships through simulated annealing and dynamic programming. J Mol Biol 212 403-428, 1990. 

MI Sutcliffe, CM Dobson, RE Oswald. Solution structure of neuronal bungarotoxm determined by two-dimensional NMR spectroscopy Calculation of tertiary structure using systematic homologous model building, dynamical simulated annealing, and restrained molecular dynamics. Biochemistry 31 2962-2970, 1992. 

Wei, D., Salahub, D. R., 1997, Hydrated Proton Clusters Ab Initio Molecular Dynamics Simulation and Simulated Annealing , J. Chem. Phys., 106, 6086. 

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