diff --git a/user-doc/tutorials/aa-lugano-6b.txt b/user-doc/tutorials/aa-lugano-6b.txt index e6d1084857ceaef299b85ae30222fa7f01877728..ae877c455ac760e295784f17baae5de2c7471156 100644 --- a/user-doc/tutorials/aa-lugano-6b.txt +++ b/user-doc/tutorials/aa-lugano-6b.txt @@ -1,15 +1,16 @@ /** -\page lugano-6b Lugano tutorial: Computing binding free energies +\page lugano-6b Lugano tutorial: Binding of a ion and a dinucleotide \section lugano-6b-aim Aims -In this tutorial I will show you how you can use PLUMED and metadynamics to compute the affinity between two molecules. +In this tutorial I will show you how you can use PLUMED and metadynamics to study the binding between a ion and a dinucleotide. \section lugano-6b-lo Objectives Once this tutorial is completed students will - Know how to enhance binding between molecules using metadynamics. +- Know how to analyze metadynamics simulations. - Know how to compute standard affinities. \section lugano-6b-resources Resources @@ -31,8 +32,88 @@ no internal degree of freedom, and instead of a protein with a complex binding p We are also assuming to know which is the proper binding site, since we can easily guess that the most stable binding will happen on the phosphate. +Since running these simulations on your laptop would take too long, you will be able to download +all the output files for a decently long simulation at this PATH. + +Before continuing, please read carefully the `plumed.dat` file since there you will find all the explanations +about which variables were biased and how. + +In case you want to do analysis with python, you can use the included `plumed_pandas.py` module, +which is a preview of a feature that will be available in plumed 2.6. +It requires pandas to be installed (use `conda install pandas`) and allows to extract +colums from a COLVAR file by name. +It works in this way: +\verbatim +> import plumed_pandas +> import matplotlib.pyplot as plt +> df=plumed_pandas.read_as_pandas("COLVAR") +# shows the head of the file: +> df.head() +# plot distance between Mg and phosphate +> plt.plot(df["dp"][:],".") +# plot coordination number of Mg with water +> plt.plot(df["cn"][:],".") +\endverbatim + \section lugano-6b-exercises Exercises +\subsection lugano-6b-ex-1 Exercise 1: Computing the free energy as a function of the biased variables. + +As the title says, just compute the free-energy landscape as a function of the biased collective variable +(namely, distance between the Mg ion and the phosphate and coordination number of the Mg ion with water oxygens). + +\subsection lugano-6b-ex-2 Exercise 2: Visualizing the trajectory + +This exercise is optional and is not needed to continue with the next points. However, it is +a very good idea to do it in order to have a better understanding of what the system is doing! + +Beware that the periodic boundary conditions were broken. You can adjust them using +PLUMED with an input like this one (please fill the gaps) + +\plumedfile +MOLINFO STRUCTURE=conf.pdb +WHOLEMOLECULES ENTITY0=@nucleic +c: CENTER ATOMS=@nucleic +mg: GROUP ATOMS=__FILL__ # find the serial number of the Mg ion +WRAPAROUND AROUND=c ATOMS=mg + +# check documentation of WRAPAROUND! +# you should also know how many atoms make a water molecule +WRAPAROUND AROUND=c ATOMS=@water GROUPBY=__FILL__ + +# dump your trajectory +DUMPATOMS ATOMS=@mdatoms FILE=whole.xtc STRIDE=10 +# writing all atoms you will be able to reuse the same pdb for opening. +# e.g. vmd conf.pdb whole.xtc +\endplumedfile + +\subsection lugano-6b-ex-3 Exercise 3: Reweighting your free energy + +Now reweight your free energy and compute it as a function of: +- distance between Mg and phosphate +- distance between Mg and geometric center of RNA +- coordination number between Mg and water + +The free energy as a function of the distance between Mg and geometric center of RNA can +be used to identify the bulk region. +In order to do so, normalize it adding the correct entropic term \f$ k_BT \log d^2 \f$, and find +a region where the free energy is approximately constant to represent the bulk region. + +- coordination number between Mg and water _assuming Mg is bound to phosphate_. +- coordination number between Mg and water _assuming Mg is in the bulk_. + + +\subsection lugano-6b-ex-4 Exercise 4: Standard affinity + +Now use the weights that you computed in the previous exercise to +compute the standard affinity of the Mg to the phosphate. In order to do +so you should compute the relative probability of seeing the Mg bound to the phosphate +and in the bulk region. + +TO COMPLETE. + +\subsection + */ link: @subpage lugano-6b