Global minimum conformation

Initially Klepeis et al. allowed the dihedral angles to vary over the entire [—7T, 7r] domain. It was found, however, that the problem required intensive computational effort (Androulakis et al., 1997). A reduction of the domain space was therefore proposed by setting limits based on the actual distributions of the dihedral angles. Obviously, for the algorithm to be successful, these reductions could not exclude the region of the global minimum conformation. 

Jerala, R., and Zerovnik, E. (1999). Accessing the global minimum conformation of stefin A dimer by annealing under partially denaturing conditions./. Mol. Biol. 291, 1079-1089. 

X-ray analysis of the 1,6-diol derivative (15) of the bicydo[4.4.1 ]-undecane ring system revealed the often calculated (9a,81) but rarely observed twist-chair cycloheptane ring. MM calculations confirmed that the observed conformation of 15 is the global minimum conformation (119). 

To imeqiuvocally demonstrate the abiHty of our procedure in successfully identifying the global minimum conformation for the boimd Hgand, the most... 

In conclusion, using high-quality STD-NMR data on UDP-Gal weakly binding to 34 GalTl, we demonstrated that it is possible to refine the crystal structure (or any computer-docked structure in the proper orientation that serves as the starting structure) to obtain a global-minimum conformation for the bound ligand in solution. 

While the fadhty and effidency of the [5+2] cycloaddition of oxygen-substituted VCPs could be attributed solely to the electronic contribution of the heteroatom substituent, it could also be a consequence of its conformational influence. Substitution of a VCP, particularly at the 1-position, has been shown to reduce the difference in energy between the s-cis (local minimum) and s-trans (global minimum) conformations through steric effects [50]. Based on the proposed mechanisms for the [5+2] cycloaddition, only the s-cis conformations, 190 and 192, can lead to productive reaction, so biasing intermediates toward this conformation could therefore accelerate the reaction (Scheme 13.16). 

Given some overall strategy of what you hope to accomplish with the calculations, you need to decide which conformation(s) of your reactant(s) to use. A potential energy surface of nontrivial molecules will have many hills and valleys. The deepest valley is called the global minimum, as mentioned earlier. Without some other basis for selecting a conformation, many chemists will want to use the global minimum conformation. However, most pertinent is the conformation a molecule adopts at the time of reaction. This may or may not be the global minimum. You may need to use your chemical intuition to choose the most relevant conformation. Sometimes, you will need to explore several different conformations. 

Carlo method [10]) enhances the chance to escape from local energy minima traps and find the global minimum conformation. 

The polar surface area of a single conformer PSAs is calculated from the global minimum conformation of the molecule (van de Waterbeemd et al. 1996, Clark 1999a). Alternatively the 3D structure of the molecule could be generated by 2D/3D converters like CONCORD (Pearlman 1987 Balducci et al.), or CORINA (Sadowski et al. 1992,1994), followed by energy minimization. Finally, the PSA of the minimized conformation is calculated for example by MOLVOL (Dodd and Theodorou 1991) or other approaches. 

Global minimum conformations within the enzyme clefts Folded conformation with the phenyl of moiety A in close proximity to the thiazo-... 

The important feature of qc p is that when a chain possesses one thermodynamically stable fold (or global minimum conformation), q p = 1 for all a and P while for a homopolymerlike collapsed globule, qap —> 1/N (indicating no stable folds or conformers). A third possibility can exist as well which typifies the spin-glass phase. The chain has numerous stable folds (or many low energy conformers). In this case, there exists a set of thermodynamically definite folds with coordinates, r, and q c = 1 when = f and q 1/N when. ... 

Wilson SR, Cui W, Moskowitz JW, and Schmidt KE (1988) Conformational analysis of flexible molecules location of the global minimum conformation by the simulated aimealing method. Tet Lett 29 4373-1376. 

It turned out in the MCRE procedure that the oligopeptide molecule always attains the global minimum conformation in the form of a two-helix bundle (see Fig. 7.14a-b), if the temperature is in a certain range. Below this range, not only the two-helix bundle, but also a (very different from the latter one) four-member /6-barrel (see Fig. 7.14c), are stable. If two protein molecules interact, one of them frozen (for whatever reasons, chemical of physical) in its metastable /6-barrel conformation, while the second molecule is free to move (Fig. 7.14d), the second molecule practically always folds to the /6-barrel that interacts very strongly with the frozen /6-barrel (Fig. 7.14e). This happens even when the second molecule starts from its native (i.e., a-helical) form the a-helical form unfolds and then folds to the -barrel (Fig. 7.14e). It bas been also demonstrated that a third protein molecule, when in the presence of the two frozen /6-barrels, folds to the /6-barrel that fits very well to the two forming a stack of three /6-barrel molecules. Formation of such stacks is notorious for prion diseases. 

Low levels of theory such as small basis set DFT or HF calculations are usually suitable for geometry optimizations and frequency calculations, provided an IRCMax approach [26] is used to correct transition structures and provided frequencies are scaled by their appropriate scale factors. When combinatorial explosion of the conformational space becomes a problem for larger molecules, our new semisyste-matic algorithm, energy-directed tree search, can reliably locate the global minimum conformation at a fraction of the cost of full systematic conformation search [27]. 

Fig. 14 Predicted low-energy conformers of proline and relative energies (MP2/6-311-H-G(d,p)) with respect to the global minimum. Conformers ate labeled as I, II, or III depending on the hydrogen bond established between the amino group and carboxylic groups. Labels aotb indicate the configuration endo (a) or exo (h) adopted by the ring. The detected conformers are encircled. (From [59, 128])...

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