Macromodel calculations

MM3-94 calculations for this work (including parameters for the NO2 group). cCalculated for this work with MacroModel 5.0 implementation of AMBER. 

Calculations by T. D. Spitzer of our group at the University of Vermont using the MACROMODEL program. 

Some results on the molecular modeling of N,N -di-methylxYlaramide (1) and IV lV -dihexYlxylaramide (2) using MacroModel V.2 are presented. Nine minimized conformers were considered and their populations calculated. Average 2 3 3 4 were then calculated and those values... 

Theoretical coupling constants for individual rotamers were obtained directly from MacroModel employing an empirical generalization of the Karplus Equation ( ). Calculated average couplings came from the expression ... 

Results From Two Sets of Calculations Using Different MacroModel Options. 

Figure 2.151. MacroModel s features include support for a variety of commonly used conformational search methodologies. Using the MacroModel interface integrated within Maestro, the user can automaticly select torsions, rotations, and translations to be explored in a calculation...

Karplus analyses of the NH-a-CH coupling constants which correlate with the characteristic torsion angle d, offer valuable information about the conformation of the peptide [17]. We compared the iJ values of the free peptides with those in the complex with their optimized binders. Usually signals became much sharper and the coupling constants markedly increased, approaching the calculated values (MacroModel). 

DECO calculations were carried out next for a double stranded polymer, using canonical B-form carbonyl geometries created by program MacroModel [21]. Without any adjustable parameters, the agreement between observed and computed spectral features was outstanding. Details of these results will be discussed along with the experimental data in Section 5. 

The VCD features for a number of larger peptide models have been calculated in the course of our efforts to define their solution conformation. These calculations proceeded exactly in the same manner as the ones described for small oligonucleotides. Cartesian coordinates from X-ray experiments, or from the program MacroModel [21), were used, along with a vibrational frequency for an unperturbed, single amide I or amide I vibration. The dipole transition moment for the amide I vibration was taken somewhat lower than that of the nucleotide base carbonyl stretching vibration, in agreement with observed data and literature values. Details of these calculations will also be provided in Section 4. 

We approached the problem of establishing a structure of the "random coil" conformation by first establishing the limits of the present computational model for a known polymeric structure, the a-helix. Coordinates, created by program MacroModel [22] for the carbonyl groups of a-helical oligomers were used, along with published and experimental dipole transition moments, to compute the VCD and absorption spectra of the a-helical conformer. We found that VCD spectra, independent of chain length, can be calculated for octamers, and that the choice of side chain residues is immaterial for the computed spectra. Both calculated and experimental data were normalized to one residue, to permit a comparison between computed and observed spectra. 

For these calculations, the carbonyl transition frequency and intensity were taken from a 1 1 CMP/GMP mixture in D20 (i/Q = 1650 cm"1 emax = 950 Lmob cm 1). Carbonyl coordinates, created by program MacroModel [21] for a canonical, B-form, alternating CG polymer, were used without geometry optimization. Band shapes were employed that are 50 50 mixtures of Lorenzian and Gaussian contours, since it was found that such a mixed composition provides the best fit between observed and computed spectra, although pure Gaussian or pure Lorenzian band shapes give satisfactory results as well. 

MS IR H-NMR C-NMR ORD [ ]d X-ray calculations (AMI, MacroModel) synthesis forms together with corianin (21) the molecular compound pseudotutin... 

The goal of the present study was to develop a computer-based cubic section model of the substrate binding domain of HLADH. It was considered that the Jones cubic section model could be refined by use of computer assisted substrate overlay in combination with kinetic data on a wide variety of substrates. As in the Jones approach we used the alcohol products as the surrogate substrate structures. Thus, we determined the low energy conformation of alcohols produced from ketones that have been reported to be reduced by HLADH and for which comparative kinetic data vs cyclohexanol could be calculated. As well, we determined the preferred conformations of all alcohols that would have been produced from ketones subjected to but failing to undergo HLADH reduction. These calculations utilised molecular mechanics (MACROMODEL) and yielded accurate co-ordinates for ali atoms in each alcohol. Where enantiomeric or stereoisomeric alcohols were produced or capable of production, the co-ordinates of each were calculated. 

Through molecular simplification, Norte et al determined that the presence of the flexible side chain was essential for the cytotoxic activity. It was further postulated that the conformation of the C14-C19 side chain was at least partially responsible for the variation in biological responses among the analogues. In order to verify this hypothesis, the stable conformations for all the compounds were determined using calculations that involved a multiconformer search using the Monte Carlo program in Macromodel and MM2 force fields [18]. 

QikProp is a software [QikProp - Schrodinger, 2003] that calculates a set of 31 physico-chemical descriptors generated by using the program MacroModel [MacroModels - Schrodinger, 1990] for —> ADME property prediction of drug candidates. The list of QikProp descriptors is given in Table Ql. 

The most rigorous dielectric continuum methods employ numerical solutions to the Poisson-Boltzmann equation [55]. As these methods are computationally quite expensive, in particular in connection with calculations of derivatives, much work has been concentrated on the development of computationally less expensive approximate continuum models of sufficient accuracy. One of the most widely used of these is the Generalized Born Solvent Accessible Surface Area (GB/SA) model developed by Still and coworkers [56,57]. The model is implemented in the MacroModel program [17,28] and parameterized for water and chloroform. It may be used in conjunction with the force fields available in MacroModel, e.g., AMBER, MM2, MM3, MMFF, OPTS. It should be noted that the original parameterization of the GB/SA model is based on the OPLS force field. 

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