View source for 2012 AMBER Tutorial with Biotin and Streptavidin

For additional Rizzo Lab tutorials see [[AMBER Tutorials]].

In this tutorial, we will learn how to run a molecular dynamics simulation of a protein-ligand complex.  We will then post-process that simulation by calculating structural fluctuations (with RMSD) and free energies of binding (MM-GBSA).

==I. Introduction==

===AMBER===
[http://ambermd.org/ Amber] - '''A'''ssisted '''M'''odel '''B'''uilding with '''E'''nergy '''R'''efinement - is a suite of about multiple programs  for perform macromolecular simulations. Amber11, the current version of Amber, includes newly released functionality such as PMEMD, particle mesh Ewald MD and soft-core Thermodynamics Integration MD. For the tutorial, we are using an older version which is AMBER10.

The [http://ambermd.org/doc10/Amber10.pdf Amber 10 Manual] is the primary resource to get started with Amber10. (Tip: Using Adobe Acrobat to view the file, you can simply search the document for keywords such as the name of a simulation parameter, which saves much time.) In addition, [http://ambermd.org/doc10/AmberTools.pdf Amber Tools User's Manual] serves as another reference while using Amber tools. You can also read the manual for Amber11 on [http://ambermd.org/doc11/ Amber11 and AmberTools Users' Manuals]

Here are some programs in Amber

#'''LEaP''': an preparing program for constructing new or modified systems in Amber. It consists of the functions of prep, link, edit, and parm for earlier version of Amber.
#'''ANTECHAMBER''': in additional to LEap, this main Antechamber suite program is for preparing input files other than standard nucleic acids and proteins.
#'''SANDER''': according to the Amber 10 manual, it is 'a basic energy minimizer and molecular dynamics program' that can be used to minimize, equilibrate and sample molecular conformations. And this is the program we mainly use in this tutorial to generate trajectory files of the molecular system.
#'''PMEMD''': version of SANDER that has improved parallel scaling property and optimized speed.
#'''PTRAJ''': an analysis program for processing trajectory files. One can use ptraj to rotate, translate the structures, evaluate geometrical features and so on. 

There is a [http://lists.ambermd.org/mailman/listinfo/amber mailing list] you could sign-up for, as an additional resource.

===Biotin and Streptavidin===
For information of the Biotin and Streptavidin system, see [[2012 DOCK tutorial with Streptavidin]].

===Organizing Directories===

While performing MD simulations, it is convenient to adopt a standard directory structure / naming scheme, so that files are easy to find / identify. For this tutorial, we will use something similar to the following:

 ~username/AMS536/AMBER-Tutorial/001.CHIMERA.MOL.PREP/  
                                 002.ANTE.TLEAP/ 
                                 003.SANDER/       
                                 004.PTRAJ/
                                 005.MMGBSA/

==II. Structural Preparation==

===Preparation in Chimera===
====Prep Structure Files====
generate structure 
 1DF8.rec.lig.pdb
 1DF8.lig.chimera.mol2
 1DF8.rec.noH.pdb
====Manually Editing Ligand Mol2 File====
A antechamber input file requires all the atom names to be unique and it only uses the first 3 characters as the name. So if we use 1DF8.lig.chimera.mol2 as the input file, it will cause errors("H102" and "H103" will have the same name "H10").
     14 O3         26.9770   10.6020   12.2050 O.2       1 BTN201     -0.6531
     15 N2         28.6480   12.1210   11.8210 N.pl3     1 BTN201     -0.4789
     16 C4         28.9670   13.2060   10.9010 C.3       1 BTN201      0.0816
     17 <font color=red>H102</font>       32.0358   17.4077   15.9597 H         1 BTN201      0.0272
     18 <font color=red>H103</font>       30.6885   18.0473   15.0102 H         1 BTN201      0.0219
     19 H92        30.5603   15.6243   15.3130 H         1 BTN201     -0.0094
     20 H93        32.1288   15.4384   14.4982 H         1 BTN201      0.0384
     21 H82        29.6624   16.7125   13.2433 H         1 BTN201      0.0275
We need to manually rename the atoms. 

visual block mode to select a rectangular section of text 
     14 O14       26.9770   10.6020   12.2050 O.2       1 BTN201     -0.6531
     15 N15       28.6480   12.1210   11.8210 N.pl3     1 BTN201     -0.4789
     16 C16       28.9670   13.2060   10.9010 C.3       1 BTN201      0.0816
     17 <font color=red>H17</font>       32.0358   17.4077   15.9597 H         1 BTN201      0.0272
     18 <font color=red>H18</font>       30.6885   18.0473   15.0102 H         1 BTN201      0.0219
     19 H19       30.5603   15.6243   15.3130 H         1 BTN201     -0.0094
     20 H20       32.1288   15.4384   14.4982 H         1 BTN201      0.0384
     21 H21       29.6624   16.7125   13.2433 H         1 BTN201      0.0275

====CP Working Directory to SW====
 scp -r AMBER-Tutorial sw:~/AMBER-Tutorial

===antechamber===

===LEaP===

===Visualization in VMD===

==III. Simulation using sander==

===Minimization and equilibration===

===Production===

==IV. Simulation Analysis==

===Ptraj===

===MMGBSA Energy Calculation===

==V. Frequently Encountered Problems==