MacroModel program

The MacroModel program of Professor C Still, Columbia University webpage... 

Fig. I. (Left) Numbering of vinblastine-type alkaloids in this chapter according to the biogenetic scheme of LeMen and Taylor (134), with equivalent atoms in all synthetic intermediates equally labeled. (Right) Approximation of computer-generated, energy-minimized structure, obtained with the Clark Still MACROMODEL program.

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

The structure of daphmanidin B (67), C25H36NO6, was elucidated by 2D NM R data to possess a l-azabicydo[5.2.2]undecane moiety, like daphnezomines F and G [46]. The relative stereochemistry was deduced from NOFSY correlations. The conformation of the unit (C-2-C-5, C-18 to C-2, C-19, and N) in the l-azabicyclo[5.2.2]undecane moiety, with a twist-chair form as shown in Figure 18.16, was consistent with the results of a conformational search using MMFF force field [60] implemented in the Macromodel program [59]. 

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. 

MM computations using the MacroModel program assisted researchers at the University of Pennsylvania and Merckxs in designing the pyrrolinone-based inhibitors of HIV-1 protease. In particular, these computations showed that 40 could adopt the 3-sheet conformation required for inhibi-... 

Addition of (16.105) and (16.106) gives the GB/SA expression for AG. The GB/SA expression is readily differentiated analytically, making it easy to use in molecular-mechanics energy minimizations (one finds the geometry that minimizes the sum of the MM steric energy and AG°oiv), and molecular-dynamics and Metropolis Monte Carlo simulations with inclusion of solvent effects. The GB/SA method is available in the MacroModel program (Section 16.6). 

In this context, we would like to emphasize the often blurred distinction between force field , the functional form and parameters, and the computer program used. The force field used by Weiner et al. (often called the AMBER force field ) has been implemented within the TRIPOS, DISCOVER, and MACROMODEL programs. In principle, the Cornell et al. force field, because of its simple functional form, could be implemented within all the programs mentioned above, with only minor modifications required in a few cases. On the other hand, for example, AMBER could not, without major changes, implement the MM4 force field. In our opinion, force field parameters, in contrast to the software in which they are used, must be made available in their entirety when an article using them is published, either in the article or an appendix or through the World Wide Web. A publication is not really science unless its results can be reproduced by others ... 

MacroModel (we tested Version 6.5) is a powerful molecular mechanics program. The program can be run from either its graphic interface or an ASCII command file. The command file structure allows very complex simulations to be performed. The XCluster utility permits the analysis and filtering of a large number of structures, such as Monte Carlo or dynamics trajectories. The documentation is very thorough. 

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>. 

We thank Professor J. L6vy for providing us with copies of Refs. 124 and 125. We also thank Professor Clark Still for a gift of the MACROMODEL computer program. Our research was supported by grant ROl-12010 from the National Cancer Institute. 

The program MacroModel contains many modified versions of other force fields, e.g., AMBER, MM2, MM3, OPLSA. ... 

II. Product Summaries Schrodinger provides its FirstDiscovery software suite to address and aid in the discovery process in industry. First Discovery runs under Unix and Linux and it includes several programs Glide, Jaguar, Liaison, LigPrep, MacroModel, Maestro, Mopac 2002, pKa predictor, Phase, Prime, QikPro, Qsite, and Strike. For the Microsoft Windows platform Schrodinger offers CAChe, BioMedCAChe, ChemFrontier, MaterialsExplorer, QikPro, Titan, and WinMOPAC. 

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. 

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