MacroModel Quick Start Guide - ISP

MacroModel Quick Start GuideChapter 5Chapter 5:Other CalculationsMacroModel has a range of other capabilities than those already encountered. This chapterprovides exercises to illustrate some of these capabilities:• Embrace—ligand binding to a receptor• Molecular dynamics• Energy profiles as a function of dihedral angles• Free energy calculations using MINTA• Partition coefficients between two solvents• Cluster analysis of structures5.1 EmbraceEmbrace is an automated routine that uses a collection of individual ligands, each pre-positionedwith respect to a given receptor. Embrace automatically performs energetic calculationson each complex formed from the receptor and the individual ligands. Embrace can work intwo modes—interaction mode and energy difference mode. In the first, the receptor and theligand are individually treated as separate sets, and only the energy components between setsare evaluated and recorded. The Embrace energy difference mode reports the minimizedenergy of both the individual ligand and receptor subtracted from the minimized energy of thecomplex. It is also possible to perform Embrace calculations using conformational searches.Embrace calculations can be accelerated by using substructures with constraints applied toatom positions. The substructure need only include elements of the protein, not any ligands.This exercise demonstrates how to import a receptor and a group of ligands, and import asubstructure and run the calculations with constraints.1. Import Embrace.mae from your working directory.If you are not sure how to import a structure, use the directions in Section 2.1 on page 5.This file contains a single protein and four pre-positioned ligands. Only the first structure,the receptor, is displayed in the Workspace.2. In the Project Table, select all of the entries.The structural input to an Embrace calculation must contain the receptor first, followedby the pre-positioned ligands. In Maestro, the receptor must be the first selected entry.MacroModel 9.7 Quick Start Guide 51