Monte Carlo conformation

R Abagyan, M Totrov. Biased probability Monte Carlo conformational searches and electrostatic calculations for peptides and proteins. I Mol Biol 235 983-1002, 1994. 

Monte-Carlo conformational analysis of the peptidomimetic perhydropyrazino[l,2-tf]pyrimidine 32a was performed using the MacroModel V 6.0 program <1999JA12204> and for 32 (R = H R" = (CFl2)2Ph, R " = Bu Y= (CH2)2C6H4-OH-/>) using MacroModel V7.1 <2002JME1395>. 

A major drawback of the PSAa is, however, the rather time-consuming calculation, particularly, the Monte Carlo conformational search, which makes PSAa inappropriate for computational screening (e-screening) of large virtual libraries. 

In view of latter developments (see Sections 16.4.9-16.4.11 for further details) the procedure, even with simplifications such as using a single CONCORD/ CORINA-derived 3D geometry instead of performing a Monte Carlo conformational search, is too computationally expensive to be applied to e-screening of virtual libraries. However, it may still be a useful alternative/complement for computing more detailed information about a compound, or to provide a more easily interpretable model to complement other models based on more rapidly computable parameters but which are difficult to interpret in terms of how to modify compounds in order for them to have better intestinal absorption characteristics. 

Fig. 4 Lowest energy conformations resulting from a Monte Carlo conformational search on an unsubstituted phenylene ethynylene dodecamer. The ideal helical conformation is shown in the lower right-hand corner. All of the other conformations are destabilized by the addition of bulky side chains...

Gouda H, Matsuzaki K, Tanaka H, Hirono S, Omura S, McCauley JA, Sprengeler PA, Furst GT, Smith HI AB (1996) Stereostructure of (-)-Chloropeptin I, a Novel Inhibitor of gp 120-CD4 Binding, via High-Temperature Molecular Dynamics, Monte Carlo Conformational Searching, and NMR Spectroscopy. J Am Chem Soc 118 13087... 

Figure 10. Top view and side view of the minimal energy conformations of the stopper-wheel complexes with trityl phenolate (left) and 3,5-di-f-butyl phenolate (right) as obtained from a 3000 step Monte Carlo conformational search with the AMBER force field. The arrows show the most favorable attack paths for the electrophile. (E+= approaching electrophile)...

For the construction of molecular structures, a 2D formula editor is provided in combination with 3D conversion. Standard potential energy minimization is performed using the modified parameter set of the CHARMm force field [68] the conformational models are built using Monte Carlo conformational analysis together with poling as described in the next section. 

Analysis of energy-minimized conformations generated using a 1000-step Monte Carlo conformational search with the AMBER force field by use of a MacroModel (version 3.5) demonstrates that both the benzothiazole ring and the carboxylic acid moieties of carbapenem 7 could be overlapped with those of 3-benzothiazolethiocephem <1997BMC601>. 

The T-shape conformation was initially hypothesized as one of the possible paclitaxel conformations in chloroform, obtained by clusterization of a Monte Carlo conformational search [36], but no ultimate conclusion about the bioactive form could be obtained solely from the ligand-based studies. Eventually, this conformation was identified as the most promising one to fit into the electron crystallography (EC) density map of paxlitaxel-bound structure [79],... 

Structure building, manipulation, comparison. SYBYL energy minimization of organic and biomolecules. Stick, space-filling, or cylinder (thick bonds) display. Interface to Chemical Abstracts Service registry files. Molfile transfer to SYBYL and Lab Vision. ChemPrint (under Windows) for 2D chemical structure drawing. PowerSearch for systematic and Monte Carlo conformational searching under Windows environment. Macintosh and PCs (DOS and Windows). 

The feasibility of coupling defects was studied with Monte Carlo conformational searches (MM3 force field, with parametrization for arylmethyl radicals) for 50 in the gas phase. The representative low-energy conformation (Fig. 30) had... 

The dynamic PSA, PSAd, was developed by Palm et al. [73]. PSAd is calculated by a Monte Carlo conformational search with subsequent energy minimization. 

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