CHEM 5412 Spring 2017: Introduction to Maestro and Linux Command Line

CHEM 5412 Spring 2017: Introduction to Maestro and Linux Command Line March 28, 2017 1 Introduction Molecular modeling, as with other computational sciences, has rapidly grown and taken advantage of the exponential growth in computational resource and tool development over the past few decades. Computational laboratory experiments become popular in many research areas including the structural biology an computational chemistry. The labs are built on the conceptual and theoretical foundation you have gained so far in this course, but the labs will also require you to delve into using modern computers in ways that you may be unfamiliar with, such as using a terminal and command-line interfaces and using technical scientific software. This lab will briefly introduce you to common command-line usage and the graphical interface of the main software tool we will use, Maestro. The Command Line Most computational science is done on Unix-based operating systems, and a large portion of this work is done using a command line interface. This semester, we will be using MacOS, and you should be able to access the command-line by either: using Finder to navigate to /Applications/Utilities and double clicking the Terminal application, or using Launcher and typing Terminal<Enter>. A new window should open, and should have the following prompt: mac-ip-addr:~ username$ From here, any commands you type will appear after the $. We have designed a small scavenger hunt based around the command line. The commands you need to complete it (along with some other helpful commands) are described below. Read through the commands below, or skip the next section to start the scavenger hunt right away. 1

2 Basic Commands Type single terminal commands with spaces separating a command and its arguments and use Enter to execute the command. Multiple commands can be entered on the same line when separated by ; (semicolon). Some common commands are listed below, grouped by category. Navigation pwd Displays your current location. Directory levels are separated by / (forward slash) cd <dir> Changes your directory. For example, cd newdir will change your directory to newdir if it exists in your current directory. The root, or top-most, directory is denoted by /. All other directories can be specified using their path relative to /, such as /home/yourname/chem5302/, which is called the absolute path of that directory. Alternatively, you can move around quickly relative to where you currently are by using the two aliases:. represents the current directory, and.. represents the current parent directory. Thus, cd.. and../../.. move you up a single directory and 3 directories, respectively. Another helpful alias is which represents your home directory. If you ever get lost, cd will take you to your home. mkdir <dir> Makes a new directory relative to the current directory. For example, cd /home/yourname; mkdir newfiles will create the directory /home/yourname/newfiles. ls <dir> Lists the contents (files and directories) of the current or specified directory. Use ls -l to get more detailed information, such as time last modified. File manipulation cp <src> <dst> Copies files at <src> to <dst>. mv <src> <dst> Moves files from <src> to <dst>. cat <file> Output all contents of a file to the terminal. less <file> Open a file for viewing. compared with cat. Allows searching and more controlled viewing when vi <file> rm <file> Open a file for editing. vi is just one of several editors. Others in Mac OS X include pico, open -e, nano, vim, emacs, and /Applications/TextEdit.app. Deletes a file. Be careful, as unlike with some other operating systems, rm does not place the deleted file in a trashcan incase you want to recover it later.

2. MAESTRO 3 rmdir <dir> Deletes an empty directory. *,? Not commands, but wildcard characters. Used to specify patterns of filenames and other text strings in use with other commands.? represents any one character, and * represents any string of characters. For example, rm *.txt will delete all files in the current directory that end in.txt. Similarly, cp../q??.maegz. will copy all.maegz files that are three characters long starting with q located in the parent directory to the current directory. (Un)Compression zip <dst.zip> <things to be zipped> Zip files into dst.zip. Add the recursive option zip -r to zip entire directories. unzip <src.zip> Unzip a zip archive. tar -cf <dst.tar> <things to be tarred> Create a tar archive dst.tar. Add the gzip option tar -czf to create a tar.gz (tgz) archive. tar -xf <src.tar> Untar a tar archive. Just as above, add -z to extract a tgz archive. Other man <cmd> Displays the manual or help page for a command. ssh <username@remote-host> Log into a remote machine using your username and password. Note that if you want to use gui-applications, use the optional flag ssh -X. scp <src-host:src-files> <dst-host:dst-files> Copy files between different computers (hosts). The two common usages are copying files to a remote machine: scp local-files username@remote.host.temple.edu:/home/username/dst, and copying files from a remote machine: scp username@remove.host.temple.edu:src-files. If you want to include directories as well as files, add the recursive optional flag: scp -R <src-host:src-files> <dst-host:dst-files> curl -O <URL> Retrieve a file from a web URL. 2 Maestro In your working directory, open Maestro by supplying the command line with its entire path: /opt/schrodinger/suites2015-2/maestro & Running commands with an ampersand (&) after them will run them in the background. This is optional.

4 Using Maestro In the main window, you should see both a row of drop-down menus (File, Edit, etc.) and row of buttons. First, let s set up the main window. Enable toolbars by selecting from the top drop-down menus: Window Toolbars. Enable the following toolbars: View Edit Let s start with a molecule that we can manipulate with Maestro. Under Edit, go to Build and select Fragments... A new window will appear titled Build. Currently this window will show Organic fragments, but in the Fragments: window, you can select other options such as Amino acids. Under Amino acids, you will see the three letter abbreviation. Click on ARG for now. Move the pointer to the view window and left-click. An arginine will appear. Close the Build window. Move and rotate the arginine around with the different mouse buttons. Note: When using Mac OSX, you may need to adjust the machine s mouse settings for 2 or 3 button mouse controls to function. To do this, open System Preferences Mouse and change the middle button to Button 3 and the right button to Secondary. While pressing the center mouse button, you can rotate the arginine around. By pressing the right mouse button, you can translate the molecule. By clicking the left mouse button while pointing at an atom, that atom will be selected. To unselect that atom, you can click the left mouse button in any blank space. Furthermore, we can manipulate the view and which atoms are selected and deleted by using the bottons on the View and Edit toolbars we enabled earlier. To recenter the atom, press the button with four arrows pointing to the corners (Fig 2.1a). If you select an atom on the arginine and press the recenter button, Maestro will center about that atom and zoom into it. To unzoom, unselect the atom and press the recenter button. You can use the delete button (Fig 2.1b) to delete atoms, molecules, etc. Left-clicking the little triangle next to the X, a drop-down menu will appear letting you delete atoms, bonds, residues, etc. with one click of the mouse in the main viewing window. Select Atoms first. By left clicking on an atom, the atom will be erased. Now select Molecules. (a) Recenter button (b) Delete button (c) Select button Figure 2.1: View Toolbar buttons

3. SIMULATION OF ALANINE DIPEPTIDE (OPTIONAL) 5 left click on any atom and the entire arginine will disappear. When finished deleting, press the delete button to turn this feature off. You can also use the select button (Fig 2.1c) to turn the delete button off. Feel free to build many molecules. One last notable feature is the Project Table. Open the Project Table using the Table button on the main menu bar (or keyboard shortcut CMD + t. There should be a single entry listed in the Project Table labeled Structure 1. This entry contains all the molecules that you placed in the workspace. You can display separate entries for each molecule by right clicking on Structure 1 and selecting Split By molecule. By clicking the square in the In column, you can toggle which molecules are displayed in the workspace (hold shift or individually include/exclude by right clicking an entry and selecting Include or Exclude). When done, select all molecules in the project table so that all entries are highlighted in yellow and press the delete key. With the window cleared, you are ready to start the first lab. Before you do, make sure you can locate the Applications menu at the top of the window. If you do not see the Applications menu, enable it by selecting: Tasks Application View. 3 Simulation of Alanine Dipeptide (optional) Building the Water Box Open Maestro. /opt/schrodinger/suite2015-2/maestro & With an empty workspace, pull up the Build window using the Edit pull-down menu. In the Build menu, select Amino acids in the Fragments menu. Then around 25 buttons for all built amino acids should appear and the ALA should be highlighted in blue. If not, click ALA. Move the mouse to the center of the viewing window and left click. A three model of alanine dipeptide will appear. This molecule will be the center around which the water box will be placed. Close the Build window. Locate the Applications menu at the top of the window. If you do not see the Applications menu, enable it by selecting: Tasks Application View. In the Applications pull-down menu, go to the Impact submenu and select Soak... A Soak window will appear. Use the default box dimension which are 18.65Åin the XYZ directions. Open the Job Settings window by clicking the gear icon beside the Run button. A Soak window will appear. Ensure that the Host is localhost. Name the job impact soak 1. Select Run. When finished, a bunch of water molecules will appear around the alanine dipeptide (zoom out or press the Recenter button). We can view the progress of our project with the Project Table by going to the Project drop-down menu and selecting Show Table (or typing CMD + T). Right now there is not a lot to see in the table. There should be one entry. To see additional information about the water box, click Show... All from the row of icons at the top of the Project Table window. The main items you will need in a later step are the dimensions of the water box: PDB~CRYST1~a PDB~CRYST1~b PDB~CRYST1~c

6 Figure 3.1: An alanine dipeptide soaked in a SPC water box Currently they should all be 18.650. The box should roughly look like Fig 3.1. You can change the representation of the water molecules by selecting under Workspace the option Molecular Representation. In the Molecular Representation window, you can set all to CPK, Tube, or Ball & Stick. The default is Wire. If you do change the representation, you must click the All button to apply the changes to the workspace. The image of this water box can be saved by clicking save image under Workspace. Energy Minimization Before performing any dynamics, we want to energy minimize the water box to take care of any overlaps that may occur in the soak process. Under Applications and the Impact submenu, select Minimization... to open the Impact Energy Minimization window. We want Use structures from: to be Workspace (included entry). There are three tabs: Potential, Constraints, and Minimization. 1. In the Potential tab, click on the Use periodic boundary conditions. Click on Settings... to the right to see the dimensions of the water box (18.650Å 18.650Å 18.650Å as shown in the Project Table). 2. Go to the Minimization tab. The defaults should be fine. You will need less than 100 cycles to relax any problems in the initial box. 3. Name the job impact mini. 4. Open the Job Settings window by clicking the gear icon beside the Run button. Make sure the Host is set to localhost. Click Run.

3. SIMULATION OF ALANINE DIPEPTIDE (OPTIONAL) 7 This will take about 10 seconds. Close Impact Energy Minimization window. When finished, notice that there is a new entry in the Project Table and that the box size has not changed. Thermalization of the Water Box to 298K Minimization tends to freeze molecules. We need to warm up the water box. We will perform a 1ps MD simulation to thermalize the waters. Go to Applications Impact Dynamics... 1. In the Impact Dynamics window, Use structure from: Workspace. 2. Under the Potential tab, make sure Use periodic boundary conditions is clicked on. 3. Under the MD Parameters, the Stop overall motion is clicked on, but Record trajectory is clicked off. We will record the trajectory later, but not for the thermalization. Set Frequency of printing information: to 100 to save disc space. 4. The Dynamics tab contains the bulk of your settings. Set Number of MD steps to 1000 (with a time step of 0.001ps, 1000 steps will be 1ps total). The Ensemble type is Constant temperature (NVT). Set the Target temperature to 298.15 K and the Temperature relaxation time (ps): to 0.20. Set the Initial temperature (K) to 100 to reflect that we are starting with a cooled box of water. In 1000 steps, the system will heat from 100K to 298.15K. 5. Open the Job Settings window by clicking the gear icon beside the Run button. Run this job locally by setting the Host to localhost. Name the job impact dyn therm1 (we will refer back to this job later). It will take under 1 minute. Production Run at 298K After completing the thermalization, you will see a new entry in the project table. Because we ran at constant volume, the box dimensions have not changed. Return to the Impact Dynamics window. Set Use structures from: to Workspace. Check to be sure in the Potential tab that periodic boundary conditions are still turned on and the box dimensions are still 18.650 3. Go to the MD Parameters tab and set frequency of printing information to 500 or 1000. Turn on Record trajectory. Change Frames written every to 1000 and turn off Sample velocities. Go to the Dynamics tab. Set the number of MD steps to 100000 (which will give us 100ps of trajectory and 100 frames in the trajectory file). Use the NVT ensemble and set the target and initial temperature to 298.15. Set the temperature relaxation time to 0.2. Start. Name it impact dyn 298. Submit this job locally by setting Host to localhost. It will take about 30 minutes. To monitor the progress of the job, you can select the button with a circle on it in the Impact Dynamics window next to the Job Settings gear icon. Once the job is complete, there will be a new entry with a blue T button in the Aux column of the Project Table. Click on the T to open the Trajectory window. At the bottom,

8 click on the Structure... button to open the Export Structure window. Export to file impact dyn 298 traj.maegz with Structures: set to Selected frames. To view the trajectory, return to the Trajectory window and press the Structure... button. Instead of exporting to a file, Export to the Project Table. The frames will be listed in the Project Table. In the second row of the project table are some round blue buttons to play through the frames in the Project Table. Press the right-pointing triangle to play forward through the frames. When everything is done, save the project by selecting Save As under the Project manu.