Starting conformation

Researchers report that high temperature molecular dynamics searches of many different starting conformations are much more efficient than using one starting structure and longer simulations. 

The second step is the molecular dynamics (MD) calculation that is based on the solution of the Newtonian equations of motion. An arbitrary starting conformation is chosen and the atoms in the molecule can move under the restriction of a certain force field using the thermal energy, distributed via Boltzmann functions to the atoms in the molecule in a stochastic manner. The aim is to find the conformation with minimal energy when the experimental distances and sometimes simultaneously the bond angles as derived from vicinal or direct coupling constants are used as constraints. 

Dependence on the starting conformation is now well established Hammond, G. S. In Reactivity of the photoexcited organic molecule, p. 119. New York Wiley. Interscience 1967. — Dauben, W. G. Plenary lecture presented at the IUPAC Symposium on Photochemistry, Baden-Baden, Germany, July 1972. 

Figure 1. a-D-Glucose in the starting conformation used herein. Hydroxyl groups are pointed clockwise, and 06 is gauche to 05 and gauche to C4 (the gg position),... 

While it is difficult to verify experimentally the calculated heights of conformational barriers, it seems that flexible-residue methods can give better results. Energies based on rigid residues increase to artificially high values at large distances from the starting < ), conformation (22). ... 

Figure 3. A comparison of two methods of producing starting conformations. With standard option -1, the conformations are generated from the preceding structure. With our -2 option, all conformations within a run are generated from the same, single starting point.

General. When possible, perform multiple simulations, making the starting conformations as independent as possible. This is recommended regardless of the sampling technique used. 

The second dataset consists of 50 V-acetyl peptide amides (Table 2) these peptides have un-ionizable side chains and have previously been studied by Buchwald and Bodor (28). The three-dimensional structures of the di-peptides were built using the force field and partial charges of Kollman (29) as implemented in Sybyl 6.5.3. The initial random starting conformations were energy minimized in vacuo. For all calculations described herein, the dielectric of the medium was set to unity and the electrostatic cut-off distance was set to 16 A. For each molecule, the Sybyl Genetic Algorithm-based conformational search,... 

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