CP2K Open Source Molecular Dynamics

User Tools

Site Tools

Trace:
exercises:2015_cecam_tutorial:urea

Differences

This shows you the differences between two versions of the page.

Link to this comparison view

Both sides previous revisionPrevious revision
Next revision		Previous revision
exercises:2015_cecam_tutorial:urea [2015/08/19 14:22] – fix file links and some markup tmuellerexercises:2015_cecam_tutorial:urea [2020/08/21 10:15] (current) – external edit 127.0.0.1
Line 2: Line 2:
  
 Problem: QM/MM study of the Urea Zwitterion in water by means of a QM/MM Hamiltonian. Problem: QM/MM study of the Urea Zwitterion in water by means of a QM/MM Hamiltonian.
 +
 +  * Original author: Marcella Iannuzzi
 +  * Complete source and output files: [[http://cp2k.org/static/exercises/2015_cecam_tutorial/UREA.tar.xz|UREA.tar.xz]]
  
 ===== Introduction ===== ===== Introduction =====
Line 25: Line 28:
   * ''RUN01_EQUIL_QMMM'' contains QM/MM NVT equilibration   * ''RUN01_EQUIL_QMMM'' contains QM/MM NVT equilibration
   * ''RUN02_QMMM_MTD1'' contains the sampling (by means of metadynamics) of the reaction from Zwitterionic to neutral form   * ''RUN02_QMMM_MTD1'' contains the sampling (by means of metadynamics) of the reaction from Zwitterionic to neutral form
-  * ''RUN02_QMMM_MTD2'' contains the sampling (by means of metadynamics) of the elimination reaction: i.e. elimination of NH$_3$ and formation of cyanic acid.+  * ''RUN02_QMMM_MTD2'' contains the sampling (by means of metadynamics) of the elimination reaction: i.e. elimination of <chem>NH3</chem> and formation of cyanic acid.
  
 The tasks we will complete in this tutorial exercise are: The tasks we will complete in this tutorial exercise are:
Line 32: Line 35:
   * Based on the averages of the NPT we will equilibrate at the NVT level with an average simulation box   * Based on the averages of the NPT we will equilibrate at the NVT level with an average simulation box
   * One the system is equilibrated at the classical Hamiltonian level we will switch to a QM/MM Hamiltonian, employing an NDDO scheme for the QM part and equilibrate further with an NVT ensemble   * One the system is equilibrated at the classical Hamiltonian level we will switch to a QM/MM Hamiltonian, employing an NDDO scheme for the QM part and equilibrate further with an NVT ensemble
-  * Study the chemical reactivity of the Zwitterion in solution: by inspecting the possibility of having a reversal reaction with formation of neutral urea or alternatively the elimination reaction, with formation of NH$_3$ and cyanic acid.+  * Study the chemical reactivity of the Zwitterion in solution: by inspecting the possibility of having a reversal reaction with formation of neutral urea or alternatively the elimination reaction, with formation of <chem>NH3</chem> and cyanic acid.
  
 ===== Theoretical Background ===== ===== Theoretical Background =====
Line 38: Line 41:
 Urea is formed in large quantities as a product of catabolism of nitrogen-containing compounds. Owing to its resonance stabilization, urea is highly stable in aqueous solutions. For example, urea spontaneously eliminates ammonia to form cyanic acid with a half life of 3.6 years at 38 Celsius degrees. Urea is formed in large quantities as a product of catabolism of nitrogen-containing compounds. Owing to its resonance stabilization, urea is highly stable in aqueous solutions. For example, urea spontaneously eliminates ammonia to form cyanic acid with a half life of 3.6 years at 38 Celsius degrees.
  
-Cyanate ion further readily undergoes conversion to CO2 and ammonia. In contrast, when catalyzed by ureases, urea is generally believed to undergo hydrolysis rather then ammonia elimination producing either HCO3- and NH4+ or ammonium carbamate, depending on the buffer system. Activation energies for urea decomposition in water at different pH have been obtained experimentally. For neutral pH, the reported activation energy ranges from 28.4 Kcal/mol to 32.4 Kcal/mol. There have been also numerous theoretical investigations of the decomposition of urea and related systems. In all of them the explicit representation of the solvent was found to be essential for detailed resolution of the mechanism, identification of the rate determining step and evaluation of the barrier. In particular in a very recent paper by Jorgensen et al. the hydrogen bonded water molecules were found to act as hydrogen shuttle for the first step of the elimination reaction. The forming zwitterionic intermediate, H3N(+)CONH(-), participates in 8-9 hydrogen bonds with water molecules and its decomposition is found to be the rate-limiting step. The overall free energy of activation for the decomposition of urea in water is computed to be  37 Kcal/mol while the barrier for hydrolysis by an addition/elimination mechanism is found to be  40 Kcal/mol.+Cyanate ion further readily undergoes conversion to <chem>CO2</chem> and ammonia. In contrast, when catalyzed by ureases, urea is generally believed to undergo hydrolysis rather then ammonia elimination producing either <chem>HCO3</chem>- and <chem>NH4</chem>+ or ammonium carbamate, depending on the buffer system. Activation energies for urea decomposition in water at different pH have been obtained experimentally. For neutral pH, the reported activation energy ranges from 28.4 Kcal/mol to 32.4 Kcal/mol. There have been also numerous theoretical investigations of the decomposition of urea and related systems. In all of them the explicit representation of the solvent was found to be essential for detailed resolution of the mechanism, identification of the rate determining step and evaluation of the barrier. In particular in a very recent paper by Jorgensen et al. the hydrogen bonded water molecules were found to act as hydrogen shuttle for the first step of the elimination reaction. The forming zwitterionic intermediate, <chem>H3N</chem>(+)<chem>CONH</chem>(-), participates in 8-9 hydrogen bonds with water molecules and its decomposition is found to be the rate-limiting step. The overall free energy of activation for the decomposition of urea in water is computed to be  37 Kcal/mol while the barrier for hydrolysis by an addition/elimination mechanism is found to be  40 Kcal/mol.
  
 The goal of this exercise will be to inspect the chemical reactivity of the zwitterion surrounded by water molecules. In this exercise, in a very simplicistic way, only urea will be considered QM while the rest of the system will be described with a classical Hamiltonian. By some high level calculations, performed in literature, it is know that the elimination mechanism, leading to cyanic acid and ammonia, happens with barrier of   5.0 Kcal/mol. The goal of this exercise will be to inspect the chemical reactivity of the zwitterion surrounded by water molecules. In this exercise, in a very simplicistic way, only urea will be considered QM while the rest of the system will be described with a classical Hamiltonian. By some high level calculations, performed in literature, it is know that the elimination mechanism, leading to cyanic acid and ammonia, happens with barrier of   5.0 Kcal/mol.
Line 60: Line 63:
     &END CELL     &END CELL
     &TOPOLOGY     &TOPOLOGY
-      CONN_FILE_NAME \${ROOT}/Files/mol_solv.top+      CONN_FILE_NAME ${ROOT}/Files/mol_solv.top
       CONNECTIVITY AMBER       CONNECTIVITY AMBER
-      COORD_FILE_NAME \${ROOT}/Files/mol_solv.crd+      COORD_FILE_NAME ${ROOT}/Files/mol_solv.crd
       COORDINATE CRD       COORDINATE CRD
     &END TOPOLOGY     &END TOPOLOGY
Line 74: Line 77:
   &MM   &MM
     &FORCEFIELD     &FORCEFIELD
-      parm_file_name \${ROOT}/Files/mol_solv.top+      parm_file_name ${ROOT}/Files/mol_solv.top
       parmtype AMBER       parmtype AMBER
       &spline       &spline
Line 90: Line 93:
   &END   &END
 </code> </code>
-In the FORCE_FIELD section we specify the same AMBER topology file, specified for the connectivity, since it stores the force-field information as well. In FIST (which is the classical module) the non-bonded potential is mapped on splines and in the spline section above, we specify the cutoff for these interactions (in this case 9 $\AA$).+In the ''[[inp>FORCE_EVAL/MM/FORCEFIELD]]'' section we specify the same AMBER topology file, specified for the connectivity, since it stores the force-field information as well. In FIST (which is the classical module) the non-bonded potential is mapped on splines and in the spline section above, we specify the cutoff for these interactions (in this case 9 Å).
  
-The core of the evaluation in a classical run, is the evaluation of the electrostatic. We can adjust these parameters in the &POISSON section (similarly to the DFT calculations). For classical runs we can employ either standard EWALD summations, Particle-Mesh Ewald (PME) sums or Smooth-Particle-Mesh Ewald ones (SPME).+The core of the evaluation in a classical run, is the evaluation of the electrostatic. We can adjust these parameters in the ''[[inp>FORCE_EVAL/MM/POISSON]]'' section (similarly to the DFT calculations). For classical runs we can employ either standard EWALD summations, Particle-Mesh Ewald (PME) sums or Smooth-Particle-Mesh Ewald ones (SPME).
  
 For this exercise we emply the SPME with a grid mesh of 54 for all 3 dimensions and the $\alpha$ parameter for the reciprocal space contributions is equal to 0.4. For this exercise we emply the SPME with a grid mesh of 54 for all 3 dimensions and the $\alpha$ parameter for the reciprocal space contributions is equal to 0.4.
  
-The control of the NPT equilibration is specified instead by the MD section:+The control of the NPT equilibration is specified instead by the ''[[inp>MOTION/MD]]'' section:
  
 <code> <code>
Line 137: Line 140:
 ===== Second task: MM isothermal ensemble ===== ===== Second task: MM isothermal ensemble =====
  
-Using the average parameters of the cell lattice, as determined in the previous run, we setup an input file to run an NVT equilibration, restarting all information but the CELL, form the previous run.+Using the average parameters of the cell lattice, as determined in the previous run, we setup an input file to run an NVT equilibration, restarting all information but the ''[[inp>FORCE_EVAL/SUBSYS/CELL]]'', form the previous run.
  
 <code> <code>
Line 159: Line 162:
 Starting from the MM system, equilibrated at the right pressure and temperature, we will start now an equilibration at the QM/MM level in the directory ''RUN01_EQUIL_QMMM''. Compared to previous input files, we need to specify everything related to the QM/MM Hamiltonian. In particular, for this system, in order to keep the computational load small, I decided to treat at the QM level only the zwitterion. We need to specify which atoms will be treated QM and also the atomic kinds of these atoms. In this tutorial example we will use SE as quantum Hamiltonian, but the extension to the DFT is immediate, since the only difference are the specification of the basis set and pseudo potential and of the proper DFT section (all these specs are not related to the QM/MM itself). Starting from the MM system, equilibrated at the right pressure and temperature, we will start now an equilibration at the QM/MM level in the directory ''RUN01_EQUIL_QMMM''. Compared to previous input files, we need to specify everything related to the QM/MM Hamiltonian. In particular, for this system, in order to keep the computational load small, I decided to treat at the QM level only the zwitterion. We need to specify which atoms will be treated QM and also the atomic kinds of these atoms. In this tutorial example we will use SE as quantum Hamiltonian, but the extension to the DFT is immediate, since the only difference are the specification of the basis set and pseudo potential and of the proper DFT section (all these specs are not related to the QM/MM itself).
  
-All the informations about a QM/MM run are specified in the QMMM section being part of the FORCE_EVAL%QMMM. In particular, we need to specify first the QM CELL. This is mandatory and important for DFT calculations (performance, correctness, efficiency) while in principle for SE runs one may use a cell as large as the MM one.+All the informations about a QM/MM run are specified in the QMMM section being part of the ''[[inp>FORCE_EVAL/QMMM]]''. In particular, we need to specify first the QM CELL. This is mandatory and important for DFT calculations (performance, correctness, efficiency) while in principle for SE runs one may use a cell as large as the MM one.
  
 <code> <code>
Line 190: Line 193:
 For this specific example, we need also to introduce an additional modification in the force-field. In fact, in the classical force-field, there is no direct Lennard-Jones interaction between the hydrogens of water and the oxygen and nitrogens of UREA. The possible collapse of the hydrogens on the Oxygen,Nitrogens is avoided by the presence of Lennard-Jones terms between Oxygen and Nitrogens of UREA and the Oxygen of water (inspect the force-field file). When performing QM/MM calculations, we may face an additional problem mainly known as electron spill-out. In fact it is possible, especially for COULOMB coupling scheme, that the electrons tend to interact in an unphysical way with the classical charges. This leads to strong attraction of classical charges inside the QM electron density. In order to avoid that, we need to implement an additional force-field term, to avoid that the hydrogens of water (extremely light) may be attracted on the Oxygen or Nitrogens of UREA, leading to a system explosion. For this specific example, we need also to introduce an additional modification in the force-field. In fact, in the classical force-field, there is no direct Lennard-Jones interaction between the hydrogens of water and the oxygen and nitrogens of UREA. The possible collapse of the hydrogens on the Oxygen,Nitrogens is avoided by the presence of Lennard-Jones terms between Oxygen and Nitrogens of UREA and the Oxygen of water (inspect the force-field file). When performing QM/MM calculations, we may face an additional problem mainly known as electron spill-out. In fact it is possible, especially for COULOMB coupling scheme, that the electrons tend to interact in an unphysical way with the classical charges. This leads to strong attraction of classical charges inside the QM electron density. In order to avoid that, we need to implement an additional force-field term, to avoid that the hydrogens of water (extremely light) may be attracted on the Oxygen or Nitrogens of UREA, leading to a system explosion.
  
-We can do that with an additional FORCEFIELD section inside the QMMM one:+We can do that with an additional ''[[inp>FORCE_EVAL/QMMM/FORCEFIELD]]'' section inside the ''[[inp>FORCE_EVAL/QMMM]]'' one:
  
 <code> <code>
Line 224: Line 227:
 ==== Homeworks ==== ==== Homeworks ====
  
-Try to convert this input to use GPW. Hints: when setting-up a correct &DFT section, keep in mind that the QM/MM multigrid approach requires the usage of COMMENSURATE grids in the &MGRID section. Moreover, instead of using the COULOMB interaction scheme for QM/MM coupling, use the GAUSS coupling. Do not forget to provide reasonable basis sets and pseudo potentials in the subsys for the QM kinds, as defined in the QMMM section.+Try to convert this input to use GPW. Hints: when setting-up a correct ''[[inp>FORCE_EVAL/DFT]]'' section, keep in mind that the QM/MM multigrid approach requires the usage of ''[[inp>FORCE_EVAL/DFT/MGRID#COMMENSURATE]]'' grids in the ''[[inp>FORCE_EVAL/DFT/MGRID]]'' section. Moreover, instead of using the COULOMB interaction scheme for QM/MM coupling, use the GAUSS coupling. Do not forget to provide reasonable basis sets and pseudo potentials in the subsys for the QM kinds, as defined in the QMMM section.
  
 ===== Fourth task: QM/MM Metadyanamics simulations ===== ===== Fourth task: QM/MM Metadyanamics simulations =====
Line 288: Line 291:
 ==== Elimination ==== ==== Elimination ====
  
-The elimination reaction is sampled along the CV representing the bond between the NH$_3$ and the HNCO moiety:+The elimination reaction is sampled along the CV representing the bond between the <chem>NH3</chem> and the <chem>HNCO</chem> moiety:
  
 <code> <code>
Line 301: Line 304:
 ===== Questions ===== ===== Questions =====
  
-Evaluate the free-energy for both processes: from Zwitterionic to Neutral form and for the elimination pathway. How do these numbers compare with the 5 kcal/mol predicted in several published works? Inspect carefully the metadynamics trajectory in order to find a solution (what is the first attempt of the hydrogen of NH3(+) before moving towards the NH(-) group? what would happen if the nearby water molecules would be treated QM?).+Evaluate the free-energy for both processes: from Zwitterionic to Neutral form and for the elimination pathway. How do these numbers compare with the 5 kcal/mol predicted in several published works? Inspect carefully the metadynamics trajectory in order to find a solution (what is the first attempt of the hydrogen of <chem>NH3</chem>(+) before moving towards the <chem>NH</chem>(-) group? what would happen if the nearby water molecules would be treated QM?).
  
 ===== Homeworks ===== ===== Homeworks =====
  
 Take into account a primary solvation shell of water molecules as a part of the QM subsystem, using a FLEXIBLE_PARTITIONING scheme to prevent the diffusion of the QM water molecules. Re-run the equilibration steps and perform the Zwitterionic-Neutral metadynamics. Do you see any change in the barrier energy? Why? Take into account a primary solvation shell of water molecules as a part of the QM subsystem, using a FLEXIBLE_PARTITIONING scheme to prevent the diffusion of the QM water molecules. Re-run the equilibration steps and perform the Zwitterionic-Neutral metadynamics. Do you see any change in the barrier energy? Why?
exercises/2015_cecam_tutorial/urea.1439994133.txt.gz · Last modified: 2020/08/21 10:14 (external edit)