Difference between revisions of "Tutorial:Glide"

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(Import and Process tab)
(Import and Process tab)
Line 116: Line 116:
 
To preprocess the structure, select the desired options, then click Preprocess. The options are as follows:
 
To preprocess the structure, select the desired options, then click Preprocess. The options are as follows:
  
     Align to—Align the protein structure to that of another protein. You can choose the other protein by selecting an entry in the Project table (Selected entry) or by specifying a PDB ID for a structure from the PDB. The alignment is done with the Protein Structure Alignment tool that is on the Tools menu—see Protein Structure Alignment Panel.
+
     To preprocess the structure, select the desired options, then click <span class="GUI">Preprocess</span>. The options are as follows:</p>
 
+
        <ul>
    Assign bond orders—This option selects the assignment of bond orders, and performs the same task as Assign Bond Orders on the Tools menu.
+
            <li value="1">
 
+
                <p class="ListPara"><span class="GUI">Align to</span>—Align the protein structure to that of another protein. You can choose the other protein by selecting an entry in the Project table (<span class="GUI">Selected entry</span>) or by specifying a PDB ID for a structure from the PDB. The alignment is done with the Protein Structure Alignment tool that is on the <span class="GUI">Tools</span> menu—see <a href="../prime_help/protein_structure_alignment.html" class="MCXref xref">Protein Structure Alignment Panel</a>.</p>
    Add hydrogens—This option adds hydrogens to all atoms in the structure that lack them. The hydrogens are added by the utility applyhtreat.
+
            </li>
 
+
            <li value="2">
    Remove original hydrogens—This option removes the original hydrogens before hydrogens are added, and is only available if Add hydrogens is selected. It ensures that any problems with H atoms are fixed, including nonstandard PDB atom names, which is important for the H-bond optimization tool.
+
                <p class="ListPara"><span class="GUI">Assign bond orders</span>—This option selects the assignment of bond orders, and performs the same task as <span class="GUI">Assign Bond Orders</span> on the <span class="GUI">Tools</span> menu. </p>
 
+
            </li>
    Create zero-order bonds to metals—This option breaks bonds to metals, replacing them with zero-order bonds, and adjusts the formal charge on the metal and the neighboring atoms. Sulfurs that interact with metals have their hydrogens removed, if necessary, and are assigned a negative charge. The force fields usually treat metals formally as an ion, without bonds to their ligands.
+
            <li value="3">
 
+
                <p class="ListPara"><span class="GUI">Add hydrogens</span>—This option adds hydrogens to all atoms in the structure that lack them. The hydrogens are added by the utility <code>applyhtreat</code>. </p>
    Create disulfide bonds—This option detects and adds bonds between sulfur atoms that are within 3.2 Å of each other. CYS residues are renamed to CYX when the bond is added. This option is selected by default.
+
            </li>
 
+
            <li value="4">
    Convert selenomethionines to methionines—This option converts selenomethionines (MSE) to methionines (MET), and is not selected by default.
+
                <p class="ListPara"><span class="GUI">Remove original hydrogens</span>—This option removes the original hydrogens before hydrogens are added, and is only available if <span class="GUI">Add hydrogens</span> is selected. It ensures that any problems with H atoms are fixed, including nonstandard PDB atom names, which is important for the H-bond optimization tool.</p>
 
+
            </li>
    Fill in missing side chains using Prime—This option allows you to add and optimize these atoms by running a Prime structure refinement job. See Predicting Side Chains for more information. If you do not select this option, you can fill in the missing side chains later, using the process described below.
+
            <li value="5">
 
+
                <p class="ListPara"><span class="GUI">Create zero-order bonds to metals</span>—This option breaks bonds to metals, replacing them with zero-order bonds, and adjusts the formal charge on the metal and the neighboring atoms. Sulfurs that interact with metals have their hydrogens removed, if necessary, and are assigned a negative charge. The force fields usually treat metals formally as an ion, without bonds to their ligands.</p>
    Fill in missing loops using Prime—Fill in missing loops from the SEQRES records in the PDB file, using Prime. The resulting loop may not be of high quality, and a Prime loop refinement should be performed to obtain higher quality. See Refining Loops for information on refining loops with Prime. If the missing residues are far from the site of interest, it might be sufficient to cap them by selecting Cap termini. (Not available from Maestro Elements.)
+
            </li>
 
+
            <li value="6">
    Cap termini—This option adds ACE (N-acetyl) and NMA (N-methyl amide) groups to uncapped N and C termini. These termini include breaks in the chains where there are missing residues. If the chain breaks are far from the region of interest, it might be sufficient to cap them. If you want to fill in the chain breaks rather than cap them, select Fill in missing loops using Prime.
+
                <p class="ListPara"><span class="GUI">Create disulfide bonds</span>—This option detects and adds bonds between sulfur atoms that are within 3.2 Å of each other. CYS residues are renamed to CYX when the bond is added. This option is selected by default.</p>
 
+
            </li>
    Delete waters beyond N Å from het groups—This option deletes waters that are more than the specified distance (in angstroms) from any het group. It is mainly useful for retaining waters that are important for ligand binding, while deleting all other waters. You can also delete selected waters in the Review and Modify tab, and delete waters that do not form hydrogen bonds with non-waters in the Refine tab.
+
            <li value="7">
 
+
                <p class="ListPara"><span class="GUI">Convert selenomethionines to methionines</span>—This option converts selenomethionines (MSE) to methionines (MET), and is not selected by default.</p>
    Generate het states using Epik—Run Epik to generate probable ionization and tautomeric states for all het groups, in the pH range specified in the text boxes. States suitable for binding to metals are also generated automatically, if the het is coordinated to a metal.This ensures that the ligands have the proper ionization and tautomeric state, which might not be assigned when using the CCD database for bond orders.
+
            </li>
 +
            <li value="8">
 +
                <p class="ListPara"><span class="GUI">Fill in missing side chains using Prime</span>—This option allows you to add and optimize these atoms by running a Prime structure refinement job. See <a class="TopicLink MCXref xref xrefTopicLink" href="../prime_user_manual/refine_proteins_sidechains.htm#refine_proteins_4294271795_98793">Predicting Side Chains</a> for more information. If you do not select this option, you can fill in the missing side chains later, using the process described below.</p>
 +
            </li>
 +
            <li value="9">
 +
                <p class="ListPara"><span class="GUI">Fill in missing loops using Prime</span>—Fill in missing loops from the SEQRES records in the PDB file, using Prime. The resulting loop may not be of high quality, and a Prime loop refinement should be performed to obtain higher quality. See <a class="TopicLink MCXref xref xrefTopicLink" href="../prime_user_manual/refine_proteins_loops.htm#refine_proteins_4294271795_92272">Refining Loops</a> for information on refining loops with Prime. If the missing residues are far from the site of interest, it might be sufficient to cap them by selecting <span class="GUI">Cap termini</span>. (Not available from Maestro Elements.)</p>
 +
            </li>
 +
            <li value="10">
 +
                <p class="ListPara"><span class="GUI">Cap termini</span>—This option adds ACE (N-acetyl) and NMA (N-methyl amide) groups to uncapped N and C termini. These termini include breaks in the chains where there are missing residues. If the chain breaks are far from the region of interest, it might be sufficient to cap them. If you want to fill in the chain breaks rather than cap them, select <span class="GUI">Fill in missing loops using Prime</span>. </p>
 +
            </li>
 +
            <li value="11">
 +
                <p class="ListPara"><span class="GUI">Delete waters beyond </span><i class="UserReplace">N</i><span class="GUI"> Å from het groups</span>—This option deletes waters that are more than the specified distance (in angstroms) from any het group. It is mainly useful for retaining waters that are important for ligand binding, while deleting all other waters. You can also delete selected waters in the <span class="GUI">Review and Modify</span> tab, and delete waters that do not form hydrogen bonds with non-waters in the <span class="GUI">Refine</span> tab.</p>
 +
            </li>
 +
            <li value="12">
 +
                <p><span class="GUI">Generate het states using Epik</span>—Run Epik to generate probable ionization and tautomeric states for all het groups, in the pH range specified in the text boxes. States suitable for binding to metals are also generated automatically, if the het is coordinated to a metal.This ensures that the ligands have the proper ionization and tautomeric state, which might not be assigned when using the CCD database for bond orders.</p>
  
 
==Grid Generation==
 
==Grid Generation==

Revision as of 10:29, 15 September 2017

(Click for lab website)

Download

To download the Schrödinger software, please visit the Download Center (login required):

  http://www.schrodinger.com/downloadcenter/

As of September 8, 2017, the current release version is 2017-3 (just released yesterday!).


Just in case, I have a copy downloaded already for Windows and MacOS, which will be provided either by USB key or CD.

It may take a while to download given its large size (about 4GB).

  Now take a break ... while downloading

Installation on your laptop

Before we start, make sure you are within the Case campus network, either by connecting through

  CaseWireless

If you are using the CaseGuest wireless, you may need to activate

  VPN

Windows-64

Start by

  1. Double-clicking setup.exe 

Wait for several seconds ... follow the instruction by clicking some 'yes' or 'next' buttons.

  2. "Installing software" ... and wait (depending on how old your laptop is) 

... after several minutes (hopefully), then clicking more 'next' using the default (unless you know what you are doing).

When you see

    "Installation completed successfully!" ... 

STOP and click

   Configure

Since we have been issued a license (installed on a server) , choose

   Add Licenses [I can identify my license server]

Enter Host Name:

   hpctest.case.edu

and Port

   XXXXX

NOTE:

   Replace XXXX with the code provided on-site

Then

   click "Save Server". 

Then check the "Current Status" above. If you see

  "Valid licenses found" 

Congratulations! You are ready to play.

Mac -- License Installation Instructions

After installation, use

  Finder, navigate to Applications → SchrodingerSuites2017-3. 

Then

   Open the Configuration application by double-clicking on it.

Since we have been issued a license (installed on a server) , choose

   Add Licenses [I can identify my license server]

Enter Host Name:

   hpctest.case.edu

and Port

   XXXXX

NOTE:

   Replace XXXX with the code provided on-site

Then

   click "Save Server". 


Then check the "Current Status" above. If you see

  "Valid licenses found" 

you are good to move on.

Getting familiar

Introduction to Structure Preparation and Visualization

This gives an introduction to the Maestro interface and basic visualization tasks. You will learn how to prepare ligand and protein structures, an essential first step for modeling projects.

    using a 3-button mouse with a scroll wheel

Creating Projects and Importing Structures

  Navigate to File > Get PDB

Visualizing Protein-Ligand Complexes

We will explore ways to visualize structures in the Workspace.

Protein Preparation Wizard

The Protein Preparation Wizard will automatically take care of many protein preparation tasks.

To open the Protein Preparation Wizard panel,

  choose Tasks → Protein Preparation and Refinement → Protein Preparation Wizard in the Task Tool, 

or

  click the Protein Preparation Wizard button on the Favorites toolbar (if present).


Import and Process tab

Click

 Preprocess


To preprocess the structure, select the desired options, then click Preprocess. The options are as follows:

   To preprocess the structure, select the desired options, then click Preprocess. The options are as follows:</p>
  • Align to—Align the protein structure to that of another protein. You can choose the other protein by selecting an entry in the Project table (Selected entry) or by specifying a PDB ID for a structure from the PDB. The alignment is done with the Protein Structure Alignment tool that is on the Tools menu—see <a href="../prime_help/protein_structure_alignment.html" class="MCXref xref">Protein Structure Alignment Panel</a>.

  • Assign bond orders—This option selects the assignment of bond orders, and performs the same task as Assign Bond Orders on the Tools menu.

  • Add hydrogens—This option adds hydrogens to all atoms in the structure that lack them. The hydrogens are added by the utility applyhtreat.

  • Remove original hydrogens—This option removes the original hydrogens before hydrogens are added, and is only available if Add hydrogens is selected. It ensures that any problems with H atoms are fixed, including nonstandard PDB atom names, which is important for the H-bond optimization tool.

  • Create zero-order bonds to metals—This option breaks bonds to metals, replacing them with zero-order bonds, and adjusts the formal charge on the metal and the neighboring atoms. Sulfurs that interact with metals have their hydrogens removed, if necessary, and are assigned a negative charge. The force fields usually treat metals formally as an ion, without bonds to their ligands.

  • Create disulfide bonds—This option detects and adds bonds between sulfur atoms that are within 3.2 Å of each other. CYS residues are renamed to CYX when the bond is added. This option is selected by default.

  • Convert selenomethionines to methionines—This option converts selenomethionines (MSE) to methionines (MET), and is not selected by default.

  • Fill in missing side chains using Prime—This option allows you to add and optimize these atoms by running a Prime structure refinement job. See <a class="TopicLink MCXref xref xrefTopicLink" href="../prime_user_manual/refine_proteins_sidechains.htm#refine_proteins_4294271795_98793">Predicting Side Chains</a> for more information. If you do not select this option, you can fill in the missing side chains later, using the process described below.

  • Fill in missing loops using Prime—Fill in missing loops from the SEQRES records in the PDB file, using Prime. The resulting loop may not be of high quality, and a Prime loop refinement should be performed to obtain higher quality. See <a class="TopicLink MCXref xref xrefTopicLink" href="../prime_user_manual/refine_proteins_loops.htm#refine_proteins_4294271795_92272">Refining Loops</a> for information on refining loops with Prime. If the missing residues are far from the site of interest, it might be sufficient to cap them by selecting Cap termini. (Not available from Maestro Elements.)

  • Cap termini—This option adds ACE (N-acetyl) and NMA (N-methyl amide) groups to uncapped N and C termini. These termini include breaks in the chains where there are missing residues. If the chain breaks are far from the region of interest, it might be sufficient to cap them. If you want to fill in the chain breaks rather than cap them, select Fill in missing loops using Prime.

  • Delete waters beyond N Å from het groups—This option deletes waters that are more than the specified distance (in angstroms) from any het group. It is mainly useful for retaining waters that are important for ligand binding, while deleting all other waters. You can also delete selected waters in the Review and Modify tab, and delete waters that do not form hydrogen bonds with non-waters in the Refine tab.

  • Generate het states using Epik—Run Epik to generate probable ionization and tautomeric states for all het groups, in the pH range specified in the text boxes. States suitable for binding to metals are also generated automatically, if the het is coordinated to a metal.This ensures that the ligands have the proper ionization and tautomeric state, which might not be assigned when using the CCD database for bond orders.

    Grid Generation

    Ligand preparation

    ==VSW==