MacroModel Quick Start Guide - ISP

MacroModel Quick Start GuideChapter 4Chapter 4:Conformational SearchesThe goal of conformational searching is to locate the low-energy configurations of a molecularstructure. MacroModel includes a number of conformational searching algorithms as well asmixed methods. This exercise first explores three standard conformational searches, thenexplores searches with the ligand/protein system prepared earlier. The final search is a largescalelow-mode search with another protein.4.1 MCMM SearchThe first conformational search is a Monte Carlo Multiple Minimum (MCMM), which generatestrial conformations by randomly adjusting rotatable bonds.1. Import MCMM.mae from your working directory.2. Choose Applications > MacroModel > Conformational Search in the main window.3. Choose Workspace (included entries) from the Use structures from option menu (seeFigure 4.1 on page 42).4. In the Substructure tab, clear any previously defined substructures and shells.5. In the CSearch tab, choose Torsional sampling (MCMM) from the Method option menu.6. Deselect Multi-ligand and Perform automatic setup during calculation.7. Click the Perform Automatic Setup button.The parameters of the calculation should be displayed as markers on the structure. If theyare not, click the Display All Markers button in the Search Variables section. Many of thevariables define conformational comparisons, which govern how the generated structuresare compared and duplicates eliminated. They can be individually examined from theparameter panels, which you open by clicking the respective parameter buttons in thecenter of the tab. The defaults are sufficient for this exercise.8. Enter 200 in the Maximum number of steps text box.9. Click Start to open the Start dialog box.10. Choose Append new entries as a new group from the Incorporate option menu.11. Enter MCMM in the Name text box.MacroModel 9.7 Quick Start Guide 41