The NRGsuite Guide Written by Francis Gaudreault Last edited on May 22, 2015 Table of Contents 1. The NRGsuite .................................................................................................................................................................. 4 1.1. Getting started ................................................................................................................................................... 5 1.2. Installing the NRGsuite ................................................................................................................................... 6 1.2.1. Installing the NRGsuite on your hard drive ........................................................................................ 6 1.2.2. Installing the NRGsuite in PyMOL .......................................................................................................... 6 1.3. The project environment ............................................................................................................................... 8 1.3.1. The hierarchy of a project .......................................................................................................................... 9 1.3.2. Creating a new project ............................................................................................................................. 11 1.3.3. Loading an existing project .................................................................................................................... 12 1.3.3. The example project .................................................................................................................................. 13 1.4. Working with the FlexAID and GetCleft interfaces .......................................................................... 14 1.5. The object/selection widget ...................................................................................................................... 15 1.6. The Wizards ...................................................................................................................................................... 16 1.7. The Validators .................................................................................................................................................. 17 1.8. The Preferences ............................................................................................................................................... 18 1.9. The About ........................................................................................................................................................... 19 2. The FlexAID interface .............................................................................................................................................. 20 2.1. Getting started ................................................................................................................................................. 21 2.2. Working with sessions ................................................................................................................................. 22 2.2.1. Saving a session ........................................................................................................................................... 23 2.2.2. Loading an existing session .................................................................................................................... 24 2.3. The Input Files tab .......................................................................................................................................... 25 2.3.1. Importing the molecules .......................................................................................................................... 26 2.3.1.1. Importing the target ...................................................................................................................................... 27 2.3.1.2. Importing the ligand ..................................................................................................................................... 28 2.3.2. Displaying the molecules ......................................................................................................................... 32 2.3.3. Resetting the molecules ........................................................................................................................... 33 2.3.4. Processing the molecules ......................................................................................................................... 34 2.3.5. Generating a 3D conformation of the ligand .................................................................................. 35 2.3.6. Changing the anchor atom of the ligand .......................................................................................... 36 2.4. The Target Config tab .................................................................................................................................... 37 2.4.1. Defining the binding-site of the target .............................................................................................. 38 2.4.1.1. Defining the binding-site using a sphere ............................................................................................. 39 2.4.1.2. Defining the binding-site using clefts .................................................................................................... 42 2.4.1.3. Pre-configured binding-sites ..................................................................................................................... 45 2.4.2. Introducing flexibility in the target .................................................................................................... 46 2.4.2.1. Adding a side-chain from the PyMOL viewer ..................................................................................... 47 2.4.2.2. Adding a side-chain by its residue code ............................................................................................... 50 2.4.2.3. Pre-configured target flexibility .............................................................................................................. 51 2.5. The Ligand Config tab ................................................................................................................................... 52 2.5.1. Including degrees of freedom for the ligand ................................................................................... 53 2.5.1.1. Including ligand translation and rotation ............................................................................................ 54 2.5.1.2. Including ligand flexibility .......................................................................................................................... 55 2.5.2. Using the ligand as reference ................................................................................................................ 57 2.5.3. Adding constraints ..................................................................................................................................... 58 2.6. The Scoring Config tab .................................................................................................................................. 62 2.6.1. Including the heteroatoms of the target .......................................................................................... 63 2.6.2. Adjusting the soft-docking properties ............................................................................................... 64 2.6.3. Adjusting the properties of the solvent ............................................................................................. 65 2.6.4. Changing the resolution of docking .................................................................................................... 66 2.6.5. Changing the sampling of rotamers ................................................................................................... 67 2.7. The Genetic Algorithm Params tab ......................................................................................................... 68 2 2.7.1. Adjusting the number of energy evaluations .................................................................................. 69 2.7.2. Adjusting the genetic operators ........................................................................................................... 70 2.7.3. Adjusting the PyMOL visual display of real-time docking ........................................................ 71 2.7.4. Changing the fitness model .................................................................................................................... 72 2.7.5. Changing the reproduction model ...................................................................................................... 73 2.8. The Simulate tab ............................................................................................................................................. 74 2.8.1. Executing a docking simulation ........................................................................................................... 75 2.8.1.1. Controlling a docking simulation ............................................................................................................ 75 2.8.1.2. Continuing a docking simulation ............................................................................................................. 76 2.8.1.3. Viewing docking in real-time ...................................................................................................................