membrane simulation

_episodes/09-Amber_flowchart.md

@@ -10,8 +10,6 @@ keypoints:
 - "To run an MD simulation with AMBER 3 files are needed: an input file, a parameter file, and a file describing coordinates/velocities . "
 ---
 
-https://github.com/ComputeCanada/molmodsim-amber-md-lesson/releases/download/workshop-2021-04/workshop_2023a.tar.gz
-
 ### Introduction
 In this lesson we will go through the steps of setting up a fully solvated protein system for simulation with AMBER/NAMD/OPENMM. There are many commercial programs and interactive graphical interfaces designed to assist with system preparation. While these tools are easy to use and don't require as much learning efforts as command line tools, they are offer only a limited functionality, and most importantly results obtained with WEB/GUI tools are not reproducible and prone to human error. When a user needs to generate multiple systems with different proteins or membrane compositions or requires different starting configurations, relying on GUI/WEB interface becomes a challenge, as the process becomes time-consuming. Therefore, we will focus on system preparation using only scriptable command line driven tools. The emphasis of this lesson is to expose you to the various methods that can be used to create a reproducible molecular modeling workflow by automating preparation and simulation steps. One of the advantages of such approach is that once a workflow script have been developed it can be easily modified for other systems or conditions (for example if an updated version of pdb file is released, you can prepare a new simulation system with a single click).
 

_episodes/13-Running_Simulations.md

@@ -84,7 +84,7 @@ The general minimization strategy is first to restrict all solute atoms with the
 {: .instructor_notes} 
 
 {: .self_study_text} 
-- it is safer to carry out several minimization steps gradually releasing restraints.
+- It is safer to start minimization with restrained macromolecules and gradually release restraints in several minimization steps.
 {: .self_study_text} 
 
 For example, we could do a two stage minimization. In the first stage we restrain all original atoms. In the second stage we restrain only the original backbone atoms. Our example protein is very small and we have limited time, so we skip the first step and restrain only protein backbone.
@@ -139,7 +139,7 @@ END
 {: .file-content}
 
 - There are several molecular dynamics programs in AMBER package: *sander, sander.MPI, pmemd, pmemd.MPI, pmemd.cuda*, and *pmemd.cuda.MPI*.  
-- *Sander* is distributed free, *pmemd* is high performance binary which requires a license.
+- *Sander* is a free CPU-only simulation engine. A high-performance simulation program is available free of charge for non-commercial use under the name *pmemd*. A license agreement must be signed by users to use.
 
 Submission script *submit.sh*:
 ~~~
@@ -188,14 +188,14 @@ In the examples bonds with hydrogens are not constrained and the default timeste
 ~~~
 Heating 
 &cntrl 
-ntt=1,                               ! Use Berendsen thermostat
-tempi=150,temp0=300,tautp=1,         ! Initial and reference temperature, time constant
-ntp=0,                               ! No barostat
-ntpr=100,                            ! Print energies every ntpr steps
-ntwx=1000,                           ! Write coordinates every ntws steps
-nstlim=10000,                        ! Simulate nstlim steps
-ntr=1,                               ! Use harmonic cartesian restraints 
-restraint_wt=10,                     ! Restraint force kcal/mol
+ntt=1,                                  ! Use Berendsen thermostat
+tempi=150,temp0=300,tautp=1,            ! Initial and reference temperature, time constant
+ntp=0,                                  ! No barostat
+ntpr=100,                               ! Print energies every ntpr steps
+ntwx=1000,                              ! Write coordinates every ntws steps
+nstlim=10000,                           ! Simulate nstlim steps
+ntr=1,                                  ! Use harmonic cartesian restraints 
+restraint_wt=10,                        ! Restraint force kcal/mol
 restraintmask="(:1-96)&(@CA,N,O)",
 &end
 END
@@ -439,13 +439,13 @@ EOF
 
 #### Generate positional restraints file for the protein backbone.
 ~~~
-gmx genrestr -f inpcrd.gro -fc 500.0 -n index.ndx -o backbone.itp<<EOF
+gmx genrestr -f inpcrd.gro -fc 500.0 -n index.ndx -o backbone.itp << EOF
 Backbone
 EOF
 ~~~
 {: .language-bash}
 
-Add definitions of the position restraints to the topology "gromacs.top". Use a text editor of your choice to insert the following lines at the end of the syste1 molecule block:
+Add definitions of the position restraints to the topology "gromacs.top". Use a text editor of your choice to insert the following lines at the end of the "system" molecule block:
 ~~~
 #ifdef POSRES
 #include "backbone.itp"
@@ -466,23 +466,19 @@ define = -D_POSRES
 {: .file-content}
 
 #### Convert AMBER restart to GROMACS restart.
-
 ~~~
 import parmed as pmd
-
 amber = pmd.load_file("prmtop.parm7", "rest.rst7")
 ncrest=pmd.amber.Rst7("rest.rst7")
 amber.velocities=ncrest.vels
 amber.save("restart.gro")
 ~~~
 {: .language-python}
 
-#### Convert GROMACS restart to portable trajectory and make binary topology
+#### Create portable binary restart (topol.tpr) file
 ~~~
-gmx trjconv -f restart.gro -o restart.trr
-gmx grompp -p topol.top  -c restart.gro -t restart.trr -f gromacs_production.mdp
+gmx grompp -p topol.top -c restart.gro -f gromacs_production.mdp
 ~~~
-- Tested with gromacs/2021 and gromacs/2022.- This procedure does not work with gromacs/2023. 
 {: .language-bash}
 
 The workshop data contains an example gromacs_production.mdp in the directory

_episodes/14-Preparing_Protein-Membrane_System.md

@@ -1,5 +1,5 @@
 ---
-title: "Preparing a Protein-Membrane Simulation System"
+title: "Preparation and simulation of membrane and membrane-protein systems"
 teaching: 30
 exercises: 5
 questions:
@@ -12,7 +12,10 @@ keypoints:
 - " "
 ---
 
-### Lipid force field
+
+## Creating simulation systems with packmol-memgen
+
+### AMBER Lipid force fields
 Amber currently includes Lipid21 as its main membrane force field.  In this modular force field, lipids are modeled as polymers composed of a headgroup and acyl tails. Essentially, this means that each headgroup and tail are independent modules, analogous to protein residues. Each lipid molecule is composed of a tail analogous to an "N-terminal", a central headgroup and another tail analogous to a "C-terminal". You can combine any headgroup with any pair of tails in this force field. Ok, now you should have an idea how the lipids are represented in the Lipid21 force field, and what lipids you can include in a simulation. 
 
 - There is a great deal of information provided in [Dickson, 2022](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007451/) regarding best practices when using AMBER for lipid simulations.
@@ -21,7 +24,10 @@ Amber currently includes Lipid21 as its main membrane force field.  In this modu
 Known Issues: 
 Using MC barostat with hard LJ cutoff is known to cause bilayer deformation. It is recommended to use an LJ force switch when running simulations with the MC barostat.[Gomez, 2021](https://onlinelibrary.wiley.com/doi/abs/10.1002/jcc.26798)
 
-### Creating simulation systems with packmol-memgen
+- To see all available lipids use  `--available_lipids_all`, but the list will have thousands of items!
+
+### Creating a membrane-only simulation system
+
 - What lipids are available?
 
 ~~~
@@ -30,9 +36,8 @@ packmol-memgen --available_lipids
 ~~~
 {: .language-bash}
 
-- To see all available lipids use  `--available_lipids_all`, but the list will have thousands of items!
 
-#### Creating a membrane-only simulation system
+
 Submission script for creating a membrane-only simulation system:
 ~~~
 #!/bin/bash
@@ -119,8 +124,13 @@ quit
 `--salt`
 
 
-### Preparing ligands 
+## Generating topologies and parameters for small molecules.
 
+### Automate Topology Builder web service. 
+[ATB](https://atb.uq.edu.au) is limited to GROMOS 54A7 force field.
+
+
+### ANTECHAMBER
 - Download hexanediol HEZ.cif: wget https://www.rcsb.org/ligand/HEZ
 - Convert .cif to .pdb: https://mmcif.pdbj.org/converter/index.php?l=en
 
@@ -155,6 +165,14 @@ saveoff HEZ hez.lib
 
 Of course point charges are not very accurate because they are derived using semi-empirical method, but antechamber can also use results of gaussian QM calculations.  
 
+### AnteChamber PYthon Parser interfacE (ACPYPE)
+
+[ACPYPE - AnteChamber PYthon Parser interfacE](https://bmcresnotes.biomedcentral.com/articles/10.1186/1756-0500-5-367). 
+
+- Simplifies the automatic generation of topology and parameters in different formats for different molecular mechanics programs.
+
+
+
 ### Links to advanced AMBER tutorials
 - [Placing waters and ions using 3D-RISM and MOFT](http://ambermd.org/tutorials/advanced/tutorial34/index.html)
 - [Building a Membrane System with PACKMOL-Memgen](https://ambermd.org/tutorials/advanced/tutorial38/index.php#Lipid_System)

setup.md

@@ -3,4 +3,5 @@ layout: page
 title: Setup
 root: .
 ---
-Download [data](https://github.com/ComputeCanada/molmodsim-amber-md-lesson/releases/download/workshop-2021-04/workshop.tar.gz)
+Download data [workshop_2023a.tar.gz](https://github.com/ComputeCanada/molmodsim-amber-md-lesson/releases/download/workshop-2021-04/workshop_2023a.tar.gz)
+