FUNCTIONALISATION, HYDRATION & DYNAMICS

Transcription

1 FUNCTIONALISATION, HYDRATION & DYNAMICS MATERIALS STUDIO TUTORIAL WAMMBAT - DAY 4

2 Our main goal: MD simulation of glucose in hydrated & functionalised silica nanopore It is not a rocket science and you can correct any outcome right away as it OCCURS. ~Axel Kohlmeyer

3 GAME PLAN 1. Introduction to Dynamics: Glucose dynamics in a water box. MSD Calculations: a) Preparation of structures & geometry optimization, Hydration in Amorphous Cell Package, NVT ensmble, b) Hydration (lower density), NPT ensemble, NVT ensemble, NVE ensemble and MSD calculation.

4 GAME PLAN 2. Glucose adsorption on functionalised silica surface: Structures preparation (silica surface, functionalisation), Hydration, NVT ensemble and MSD calculation.

5 GAME PLAN 3. Glucose dynamics in functionalised silica pore due to MSD calculation: Preparation of structures, - pore multiplication, - functionalisation, - glucose insertion, Hydration, Dynamics.

6 Before we start A bit of theory...

7 MSD

8 MSD <r 2 > T 2 T T 0.5

9 MSD caging regime diffusive regime balistic regime

10 MSD

11 MSD MSD Time...

12 MSD MSD Time...

13 MSD MSD Time...

14 MSD MSD Time...

15 MSD MSD Time NO DATA

16 MSD MSD Time NO DATA NO DATA

17 MSD MSD Time

18 MSD

19 MSD

20 CVFF The Consistent-Valence ForceField is a generalized valence forcefield. Parameters are provided for amino acids, water, and a variety of other functional groups.

21 CVFF pot = D b [1 e α b b 0 b ሿ 2 + H θ (θ θ 0 ሻ 2 + H φ [1 s cos nφ θ φ ൧ + H X X 2 X energy of deformation of bond lengths, bond angles, torsion angles and out-of-plane interactions + F bb b b 0 b b 0 + F θθ θ θ 0 θ θ 0 b b θ θ + F bθ b b 0 θ θ 0 + F φθθ cos θ θ 0 θ θ 0 + b θ φ X X F XX XX vibrational frequencies and the dynamic properties of molecules + σ ε [ r r 12-2 r r 6 ] + q iq j εr ij non-bond interactions

22 CVFF pot = D b [1 e α b b 0 b ሿ 2 + H θ (θ θ 0 ሻ 2 + H φ [1 s cos nφ θ φ ൧ + H X X 2 X + F bb b b 0 b b 0 + F θθ θ θ 0 θ θ 0 b b θ θ + F bθ b b 0 θ θ 0 + F φθθ cos θ θ 0 θ θ 0 + b θ φ X X F XX XX + σ ε [ r r 12-2 r r 6 ] + q iq j εr ij

23 COMPASS Condensed-phase Optimized Molecular Potentials for Atomistic Simulation Studies is the first ab initio forcefield that enables accurate and simultaneous prediction of gasphase properties (structural, conformational, vibrational, etc.) and condensed-phase properties (equation of state, cohesive energies, etc.) for a broad range of molecules and polymers. It is also the first high quality forcefield to consolidate parameters of organic and inorganic materials.

24 COMPASS COMPASS COMPASS II Atom Types Forcefield Terms

25 MD software There are lots of MD programs, may not as graphically sophisticated as Materials Studio, but professional likewise. MD scientist's work is always divided into several steps and often executed with different software, for example: - building crystal (with or without the pore), - hydration, - optimalisation, - dynamics, - results analysis and presentation (visualisation). Each program propose different opportunities and in some way is hardly replaceable in it's special field.

26 MD software Materials Studio allows user to perform all the steps, but sometimes other specific parameters or functions are necessary and usage of more adjustable software is vital. List of paramters that might be set and possibilities of changes is often more available than in commercial software, but user is demanded to know much more about how program works. Major part of MD software is OpenSource and required changes are possible straight from the source. fragment of LAMMPS source code

27 Geometry optimization Each system must be optimized before your proper simulation. Every algorithm leads potential energy function to its minimum. You must be aweare that potential energy is rather multidimensional hypersurface than 3D function (seen on the pic.). Initial energy Global or local minimum

28 Geometry optimization Example of convergence criteria: 1. Convergence of the function (energy) f x k+1 f(x k ሻ < ε f 2. Convergence of the variable (position) x k+1 x k < ε x 3. Covergence of the gradient (force) Initial energy Global or local minimum f x k+1 f(x k ሻ < ε g

29 Geometry optimization Examples of most popular energy minimization algorithms: - conjugate gradients, - steepest descent. And also some damping dynamics algorithms such as: - quickmin, - fire. Initial energy Global or local minimum

30 Potential energy Geometry optimization 60º 109.5º 145º 180º 215º 215.5º 300º Angle

31 PART 1 - Introduction The first task is to create the whole system: molecule in water. Usually it is a very time-consuming step during the whole research process. This example is very simple, but imagine some more complicated biological systems as presented on the picture. Each step may be done in few different approaches. One of them is our goal: hydration.

32 Periodic Boundary Conditions

33 Goal: glucose in water no PBC Glucose PBC addition Water addition

34 Goal: glucose in water no PBC No problems with non-bonded interactions Huge number of atoms Expensive PBC Atom may interact with itself Small number of atoms Cheaper

35 Example: Hydration by packmol Packmol is an opensource project developed for quick biosystem building. It does not have it's own graphical interface and should be run in system shell. Our group logs into BEM cluster and performs calculations there in command line by Secure Shell (SSH). During WAMMBAT we have already used BEM cluster by Materials Studio gateway due to the hospitality of WCSS team.

36 Example: Hydration by packmol How it works? 1. User defines box sizes and number of molecules (each kind). 2. Packmol guesses positions of all the molecules as they were balls of selected radius (tolerance). 3. Packmol tries to calculate better coordinates to fit all the particles into selected box and stops while tolerance is reached. Final structure is set of geometrically fitted molecules, so it's geometry should be optimized with proper forcefield.

37 After packmol hydration Geometry Optimization includes forces and optimize geometry NPT ensemble density (volume) equilibration NVT temperaturę equilibration

38 Example: Amorphous Cell - Packing geometry optimization + next step geometry optimization + next step

39 Example: Amorphous Cell - Packing after a while..

40 Pros and cons of both methods parameter Packmol Amorphous Cell - Packing Handling Difficulty low-medium very easy Graphical Interface text-mode (unix systems) module built in MS Computation Efficiency very efficient even in really huge systems only small systems Geometry Optimization no automatic Density Control user defines number of molecules --> system needs equilibration of density automatic

41 Queueing An imprortant issue is PBS - the queue system. Any job before running on BEM (or any other cluster) has to be queued. User must define computing resources (number of parallel processors, RAM memory, time of reservation) and some additional parametrs, then is given specified priority by the queue system. Materials Studio gateway does it automatically.

42 Queueing User Gathering results Queue system Hardware

43 Queueing

44 Queueing User Job Priority Queue Hardware - Memory - Nodes - Max time - length - available slots - resources (nodes, memory) - user priority

45 Queueing 12 nodes 1/12 in use Requested resources 12 nodes Find available slots 11/12 3/12 8/12 1/12 12/12 12/12 12/12 12/12 12/12 12/12 12/12 12/12 12/12 12/12 12/12 7/12 12/12 12/12 12/12 12/12

46 WCSS

47 Goal: glucose in water Glucose PBC addition Water addition

48 Clean up the scene Tousands of constantly opening windows during work in Materials Studio may be very annoying, so please remember to uncheck Automatically view output checkbox in more menu in Job Control tab before you start any job.

49 Clean up the scene The most important issue is not to be lost in data mess. First of all we'll manage all the files created through the last days. - Open Materials Studio and your wammbat project. - Create a new folder in the main location: Day 4 - Dynamics and Create new folders Task 1, Task 2, Task 3 inside it.

50 Clean up the scene Find and paste proper files from last days: Task 1 Task 2 Task 3 glucose (Day 1) glucose+.xsd (Day 3) glucose+.xsd (Day 3) Si-2NH3.xsd (Day 3) functionalised silica pore (Day 2)

51 Clean up the scene For both crystal structures change representations to Constraint and check if crystal part is fixed. functionalised silica pore (Day 2) Si-2NH3.xsd (Day 3)

52 Structures preparation Open a new 3D Atomistic document in Task1 folder. Name it water cvff. Draw Oxygen atom using Sketch atom and update hydrogens.

53 Structures preparation Before water molecule will be ready to use it should be optimized in forcefield that will be used afterwards. Set Geometry Optimization task and More... options as presented. Open Forcite Calculation.

54 Structures preparation Materials Studio modules (Forcite, Amorphous Cell and others) "remember" the last used properties. You can open different document and be sure the settings are set exactly the same as in the previous document. If you see: "set as presented" on the tutorial page, it means for 90% that we used this module before and it does not require any changes.

55 Structures preparation In Energy tab set cvff Forcefield, Forcefield assigned charges, Medium quality, Atom based Electrostatic and van der Waals. In Job Control tab set one core.

56 Downloading your results To download results after a job is completed rightclick on the job, select Actions --> Download Results

57 Structures preparation Without closing Forcite window open glucose molecule and RUN optimization again.

58 Structures preparation You can rename and move optimized Water and glucose documents to the Task1 folder and delete other files.

59 Structures preparation To build a box: Open Build --> Crystal --> Build Crystal... Set Lengths in Lattice Parameters tab to 20 Angstroms and click Build. Concentration of glucose in this box: 0.2 M. C = n V = mol dm 3 = M

60 Hydration in Amorphous Cell To pack water inside the box, open: Amorphous Cell --> Calculation module. Select Packing task, Density to 1,0 g/cc, Output to 4 frames and set water opt as a Molecule. Open Options menu.

61 Hydration in Amorphous Cell Set options as presented. In previous menu you set 4 frames for output. Sometimes system after packing may have extreme energy and explode. Usually temperature, pressure and density is reached gradually to prevent such situations. In this tutorial we try to save time and prepare 4 structures in case of explosion.

62 Hydration in Amorphous Cell In Energy tab set Ewald in Electrostatic summation During this task MS cannot divide your box into a few smaller boxes, so you cannot use more cores.

63 NVT ensemble System is ready to carry on the dynamics calculations. Open Forcite Calculation. Choose Dynamics and open More... menu.

64 NVT ensemble In Dynamics tab set: NVT ensemble, Random velocities, 298 K, 1,0 fs time step and 130 ps total simulation time. To obtain a detailed plot, set an output frame every 200 steps. In Thermostat tab choose Nose thermostat.

65 NVT ensemble Go back to main menu, and in Energy tab set PPPM electrostatic summation and Ewald van der Waals. Remember to set maximum available core number in Job Control properties. Then click Run.

66 Ewald summation method Ewald summation is an algorithm wich effciently calculates the interactions between periodic mirrors of atoms or molecules. Van der Waals interactions deacys like 1 r 6 so there is no porblem usually periodic mirrors are over the cutoff. In case of Coulomb electrostatic interactions k q iq i_mirror r i i_mirror potential deacys slow. Ewald proposed 1 + which states for short range, rapidly varying function r r and long range flat function. The f r = erfc r = 2 π x exp t 2 dt. = f r r 1 f r

67 Ewald summation method Reciprocal space Real space r r Each charge is neutralised with neutralising charge Another contribution counteracts neutralisation Real space r

68 Particle-particle particle-mesh In the particle-particle particle-mesh method (PPPM, P 3 M) some simplifications are made. Beyond some distance R c particles (atoms) are discetized charge density gives a contribution to neighbouring grid nodes. For close particels (atoms) interactions are calcualted by common Ewald summation. Mesh grid

69 Ewald vs. PPPM (P3M) Ewald summation Summation over every atom Uses Fourier transform Particle Particle Particle mesh Summation over a discretized grid of charge denisty Uses fast Fourier transform Faster for smaller systems Significantly faster for large systems (N > 10000ሻ # Atoms Ewald (c. time) P3M (c. time)

70 But in real work...

71 Dynamics Calculation stages to define temperature and density NPT NVT NVE equilibration of density (volume changes) equilibration of temperature final dynamics

72 Thermostating & Barostating Simulation system is dynamical. In order to preserve the system specific temperature or pressure we employ in the calculation the concept of thermostat and barostat. Conceptionaly these are separate systems with defined pressure an temperature connected to our simulation balls. Mathematicaly we simply add two Newtons equations, additionaly equations defining temperature and pressure.

73 Berendsen Thermostat The velocities are scaled at each step, such that the rate of change of temperature is proportional to the difference in temperature. Scaling factor:

74 Berendsen Barostat. In barostat the mechanism is similar: Scaling factor:

75 NPT V nt/p During simulation ensemble uses barostat and thermostat to equilibrate temperature and pressure. Varying, operating both: P and T results in changes of volume of the simulation box. In other words, our goal is to reach density of water about 1.0 g/cc, that is a property of our system in 298 K and 1 bar.

76 NPT Box length running average

77 NPT Density

78 NVT High kinetic energy equilibrated temperature Running average Random Velocities High potential Energy Temperature Strong thermostat work

79 NVE

80 New system In Task 1 folder open glucose cvff.xsd document. Prepare Packing exactly the same as last time except density, set it to 0.8 g/cc. Click Run.

81 NPT ensemble System is ready to carry on dynamics. Open Forcite Calculation. Choose Dynamics and open More... menu.

82 NPT ensemble In Dynamics tab choose NPT ensemble, 1,013e-4 GPa pressure, 1,0 fs time step, 8 ps total time and output every 20 steps. Thermostat tab leave without changes. Set Berendsen barostat.

83 NPT ensemble Go back to previous menu and set PPPM Electrostatic and Ewald vdv. Remember to set maximum core number in Job Control tab. Run dynamics.

84 NPT ensemble Open plots and check if simulation time was sufficient to equilibrate density in your box.

85 NVT ensemble Open Forcite Calculation. Choose Dynamics and open More... menu. Check Restart box. Forcite will take final velocities from NPT dynamics.

86 NVT ensemble In Dynamics tab set NVT ensemble, 8,0 ps total simulation time and output every 20 frames. Thermostat leave without changes. Move back to the main Forcite menu.

87 NVT ensemble Rest of the tabs leave without changes and Run dynamics.

88 NVT ensemble Open plots and check if simulation time was sufficient to equilibrate temperature inside your box.

89 NVE ensemble Open Forcite Calculation. Choose Dynamics and open More... menu.

90 NVE ensemble As you see, in NPT we set Dynamics, Thermostat and Barostat properties. In NVT there was no Barostat, and now in NVE ensemble there is neither Barostat nor Thermostat. Set NVE ensemble and 130ps in total simulation time. Set output every 140 steps.

91 NVE ensemble Rest of the tabs leave without changes and Run dynamics.

92 Calculate MSD Materials Studio store all data about dynamics, so different calculations might be performed any time it is needed. Now, we will perform MSD analyse for both tasks. Make sure if you have opened proper xtd document before you start analysing.

93 Calculate MSD Materials Studio store all data about dynamics, so different calculations might be performed any time it is needed. First of all select glucose by shift+double click. Then Edit --> Sets

94 Calculate MSD Make sure you have opened proper file and open Forcite --> Analysis and choose mean square displacement (MSD) Set origin to the begining of simulation and using arrows set length frames to about the 2/5 of simulation time. Now Analyze.

95 Calculate MSD Diffusive regime

96 Calculate MSD Calculations resulted with two new documents - plot and data table. Open Table and select B column. Open Statistics --> --> Model Building --> Multiple Linear Regression

97 Calculate MSD Select Time and click OK. Here is your result.

98 Calculate MSD D[ m2 A 2 your result [ s ሿ = ps ሿ

99 Calculate MSD Do it again with second simulation results!

100 You didn't receive ? :(

101 Confined Diffusion

102 Diffusion parameter - concentration - thermostating - forcefield - system size - randomness in three dimensions - temperature - accuracy -...

103 Diffusion Parameter Really, really short simulation Proper order of magnitude! Result similar to reality!

104 It's high time we started our second task!

105 PART 2 - Glucose adsorption We will repeat Monte Carlo project using Dynamics instead. We will also hydrate our system. Due to the periodic boundary conditions and very small scale we can simplify the pore to the silica layer with water above.

106 Goal: Box with glucose and water Box Box + glucose Water addition

107 Prepare silica layer There are some structures in Task 2 folder already: - glucose+.xsd, - Si-2NH3.xsd.

108 Structures preparation Open a new 3D Atomistic document in Task2 folder. Draw Oxygen atom using Sketch atom and update hydrogens.

109 Structures preparation Open Forcite Calculation. Set Geometry Optimization task.

110 Structures preparation In Energy tab set COMPASS II Forcefield.

111 Structures preparation Paste glucose into the box and move it to a proper destination using toolbar.

112 Solvent surface 1A ball radius 2A radius vdw surface vdw radius 2A solvation surface

113 Solvent Surface exclude too-close (high energy) locations exclude crystal inside

114 Prepare hydration surface To create hydration surface open: Tools --> Atom Volumes & Surfaces and choose Task: Solvent surfaces. Then Create surface.

115 Prepare hydration surface The last step is to inverse hydration surface to set high values inside the surface, that results afterwards in packing the surface's outher part. Select isosurface bu double click, right click and choose Display Style --> Isosurface tab Select High values inside checkbox.

116 Pack water inside the box Amorphous Cell Packing module packs molecules one after another and optimalise whole system geometry. To pack water inside the box, open: Amorphous Cell --> Calculation module. Select Packing task, Density as 1,0 g/cc, and water Molecule. Open Task --> more menu and check Pack in isosurface enclosed volume. Open Options menu.

117 Pack water inside the box Packing parameters are probably set by default, but make sure they are set correctly. Open Options menu and select: parameter Torsions Temerature value calculate automatically 298 K Loading steps 1000 Check energies Optimize geometry select select

118 Pack water inside the box Energy and Job Control tabs are already set. You should only change forcefield to COMPASS II. Now you can Run packing.

119 Pack water inside the box Select isosurface and delete it. It is no longer neccesary. Now, you are ready to run dynamics calculations.

120 NVT ensemble Open Forcite Calculation. Choose Dynamics and open More... menu.

121 NVT ensemble To observe diffusion the simulation time has to be of the order of nanoseconds. Now set the Total simulation time as 5,0 picoseconds to examine whole process. Afterwards, calculations will continue for the whole night. To equilibrate temperature time about 120ps is far enough. Afterwards, dynamics will be continued for 1ns in NVE ensamble and results of the analysis will be conducted tommorow.

122 NVT ensemble Go back to previous menu, check Energy tab and Run dynamics.

123 Dynamics As you noticed before, each job has it's own folder. Check what files they contain. Open the temperature plot. It presents that the thermostat works in a proper way. The temperature optimization will be continued. To start it please use prepared script that will run NVT and NVE simulations one after another.

124 Continue dynamics We equilibrated temperature and system is ready for NVE ensemble, but the rest of dynamics we will continue in the end of today laboratories.

125 PART 3 - Glucose dynamics The last task is to functionalise and hydrate complete silica pore. The dynamics, that we will start today will continue the whole night and will be analysed tomorrow.

126 Goal: Pore with glucose and water silica preparation functionalization water addition

127 Clean up the scene again Check if you recognise all the subfolders names in your catalog tree. Change names if necessary. The way you order your project should be suitable for easy navigation for you, but we recommend to follow us:

128 Put glucose inside the pore To put glucose inside the pore select deprotonated glucose, that was optimized in COMPASSII forcefield and paste it into your pore. Select glucose by shift+click and move using moving toolbar. -NH3 -COO -NH3 -COO Be careful to put glucose in between ("z" direction) NH3 groups and COO- groups and in the center of the pore tunnel. : -NH3 (the same)

129 Prepare hydration surface It is time we did hydration surface exactly the same as in Task2: Open functionalised silica document from Task 3 folder. Open Tools --> Atom Volumes & Surfaces and choose Solvent surfaces task. Then Create surface.

130 Prepare hydration surface The last step is to inverse hydration surface to set high values inside the surface, that results afterwards in packing the surface's outher part. Select isosurface bu double click, right click and choose Display Style - -> Isosurface tab Select High values inside checkbox.

131 Pack water inside the box To pack water inside the box, open: Amorphous Cell --> Calculation module. Select Packing task, Density as 1,0 g/cc, and water Molecule. Open Task --> more menu and check Pack in isosurface enclosed volume.

132 Pack water inside the box Open Task --> more menu and check Pack in isosurface enclosed volume. In Energy tab set COMPASS II Forcefield, Charges Forcefield assigned, Quality Medium and Ewald Electrostatic summation method. Now you can Run packing. Remember to delete isosurface while packing is finished.

133 Dynamics Our structure is to big to be calculated as fast as before. The dynamics will continue for the whole night. In Forcite Calculation --> Dynamics set NVE ensemble, 1 fs timestep, 500 ps total time, and frame output every 500 frames. In Job Control tab select 2 cores. Now, open Task 2 ready structure. In Dynamics options set 1000ps total time and Run again.

134 CAUTION! Our calculations will be continued so please DO NOT log out or shut down your computer till tomorrow!

135 To be continued...