Molecular Dynamics and Conformations

Graphical molecular modeling package. MULTIC for molecular mechanics, molecular dynamics, and conformational searching of organic molecules, proteins, nucleic acids, and carbohydrates. AMBER-, MM2-, and MM3-like and OPTS force fields implicit solvation model. Reads Cambridge and Brookhaven PDB files. VAX, Convex, Alliant, Cray, and UNIX workstations. 

Homology modeling using simulated annealing of restrained molecular dynamics and conformational search calculations with CONGEN application in predicting the three-dimensional structure of murine homeodomain Msx-1. 

H. Grubmueller and P. Tavan. Molecular dynamics of conformational substates for a simplified protein model. J. Chem. Phys. 101 (1994)... 

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. 

W. L. Jorgensen and J. Tirado-Rives, Monte Carlo vs molecular dynamics for conformational sampling. J. Phys. Chem., 100, 1996, 14508-14513. 

An additional point illustrated in this paper is the usefulness of high resolution NMR techniques in examining elastomer gels. This provides a relatively simple approach to dynamic and conformational information at a basic molecular level. The interpretation of the data in terms of a complete picture of molecular motion may be complicated by the nature of the distribution of motional modes, but by sampling at a variety of frequencies of different nuclei and at different magnetic fields it should be possible to develop a more accurate picture than we have been able to present here. 

Using molecular dynamics and free energy analyses to calculate the free energies of binding and conformational change, J. Mol. Biol. 297 1145 (2000). 

Hudson, B. D., George, A. R., Ford, M. G., and Livingstone, D. J. (1992) Structure-activity relation ships of pyrethroid insecticides. Part 2. The use of molecular dynamics for conformation searching and average parameter calculation.. /. Comput-Aided Mol. Design 6, 191-201. 

Molecular dynamic and NMR studies have shown that only the extended conformation of CF3-acetyldocetaxel (i.e., in which the isoserine side chain is distant from the baccatine moiety) is independent of the hydrophilic or hydrophobic nature of the medium. In the other derivatives of Taxol, the globular conformation is largely favored by a protic medium. " Thus, it would be interesting to perform studies of complexes with tubuhnes in the solid phase to determine if the cytotoxic activity is connected with the conformation. 

The main driver behind developing LFMM is computational efficiency. Although DFT has undoubtedly revolutionized the theoretical treatment of TM systems, there are many instances where all QM methods, even DFT, are simply not viable. Comprehensive conformational searching, molecular dynamics, and virtual screening represent hundreds of thousands of individual calculations and QM methods are too expensive. We are forced to turn to classical models but, for TM centers, this presents a whole new set of challenges. However, since we cannot easily make QM orders of magnitude faster, our only option is to make MM smarter and thus able to cope with the extra demands of coordination complexes. 

G-Protein-coupled receptors do not lend themselves to analysis by either NMR or x-ray crystallography due to their structural dependence on an intact cell membrane. In our laboratories we pursued this valuable structural information by utilizing a combination of structural homology modeling, molecular dynamics, systematic conformational searching methods, and mutagenesis experiments. The combination of these techniques led to a proposed model of bradykinin bound to the agonist site on its receptor [41]. 

A theoretical approach is applied to elucidate the molecular conformations, associated flexibility, and dynamics of polylp-hydroxybenzoic acid) esters, pHB. Properties such as the radius of gyration and persistence length which are characteristic for the stiffness of a macromolecule are calculated on the basis of two different theoretical methods (a) Molecular dynamics and (b) the RIS model augmented by the more recent scheme for the matrix computations. The analysis of the results obtained by the latter method reflects a strong dependence on the choice of the structural parameters of the system. 

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