Low-mode conformational search

L, Guida W. C. Low-mode conformational search elucidated Application to C39H80 and flexible docking of 9-deazaguanine inhibitors into PNP. /. Comput. Chem. 1999, 20,1671-1684. 

The selectivities were calculated using the Boltzmann distribution, based on the energies of the most stable conformations. The authors performed a conformational analysis for each of the 12 different pathways of approaching of the olefin to the osmium tetroxide. They combined two techniques, the pseudo-systematic Monte Carlo [65] to explore the entire conformational space, and the Low Mode [66] searching to explore exhaustively a local region of the potential energy surface (Table 2). 

A particular advantage of the low-mode search is that it can be applied to botli cyclic ajic acyclic molecules without any need for special ring closure treatments. As the low-mod> search proceeds a series of conformations is generated which themselves can act as starting points for normal mode analysis and deformation. In a sense, the approach is a system ati( one, bounded by the number of low-frequency modes that are selected. An extension of th( technique involves searching random mixtures of the low-frequency eigenvectors using Monte Carlo procedure. 

The molecule preparation step includes also conformational expansion using a torsional search or a combined Monte Carlo Multiple Minimum/Low Mode search. During the search, the intramolecular hydrogen bonds are not considered. Molecules can be minimized, OPLS-2005 or MMFF force fields [86, 87] are available, and also two continuum solvation models (distance-dependent dielectric or GB/SA). A double criterion is used to eliminate redundant conformations it uses distances between pairs of corresponding atoms within a 1 kcal moh1 energy window. 

Kolossvary I and W C Guida 1996 Low Mode Search An Efficient, Automated Computational Method for Conformational Analysis- Application to Cyclic and Acyclic Alkanes and Cyclic Peptides Journal of the American Chemical Society 118 5011-5019. 

The main conclusion from our study on molecular property similarity searching is that it is useful for discovering new substance classes for a bioactivity, assuming the. same basic mode of action as the query substance. It seems to be effective even though only one low energy conformer is the basis... 

LMOD operates in neither torsion space nor Cartesian space, nor any other user-defined search space LMOD generates its own search space LMOD determines the low-mode search directions in conformational space automatically and is appropriate for any kind of molecular systems including rings and molecular complexes. LMOD is inherently well suited for conformational searching of complexes, because the relative translations and rotations necessary to guide one molecule with respect to the other(s) appear as low-frequency vibrations on the intermolecular PES. 

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