Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models D AMMIF Update Get the latest version of D AMMIF together with the latest release of ATSAS! ATSAS 2.5.0 will be available soon! http://www.embl-hamburg.de/biosaxs/download.html Daniel Franke — Ab-Initio Modelling 1/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models Ab-Initio Modelling D AMMIN and D AMMIF Daniel Franke European Molecular Biology Laboratory 2012/10/19 Daniel Franke — Ab-Initio Modelling 2/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models The following slides describe the how, not the why! Daniel Franke — Ab-Initio Modelling 3/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models Outline Introduction 1 Ab-Initio Modelling 2 3 Obtaining Models Postprocessing Models 4 Daniel Franke — Ab-Initio Modelling 4/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models Basic Idea Find a three dimensional object whose theoretical scattering curve would resemble the experimental data best. Daniel Franke — Ab-Initio Modelling 5/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models Results Daniel Franke — Ab-Initio Modelling 6/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models The Dummy Atom Model Many little scatterers ... A Dummy Atom Model (DAM) is build by a tightly packed group of dummy atoms. The volume occupied by dummy atoms in any state (particle, solvent) is also known as search volume. Daniel Franke — Ab-Initio Modelling 7/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models The Dummy Atom One little scatterer ... Acts as a placeholder for, but does not resemble, a real atom Occupies a known position in space Has a known scattering pattern May either contribute to the solvent or the particle Dummy atoms are also referred to as beads. Daniel Franke — Ab-Initio Modelling 8/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models Basic Idea Revisited. Find a three dimensional object whose theoretical scattering curve would resemble the experimental data best. Find the set of dummy atoms within a search volume whose accumulated scattering resembles the experimental data best. Daniel Franke — Ab-Initio Modelling 9/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models Basic Idea Revisited. Find a three dimensional object whose theoretical scattering curve would resemble the experimental data best. Find the set of dummy atoms within a search volume whose accumulated scattering resembles the experimental data best. Daniel Franke — Ab-Initio Modelling 9/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models Validity of Input Garbage In – Garbage Out Validate input data; check for aggregation at the beginning noise at higher angles Remember: noise can be modelled nicely Daniel Franke — Ab-Initio Modelling 10/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models Outline Introduction 1 Ab-Initio Modelling 2 3 Obtaining Models Postprocessing Models 4 Daniel Franke — Ab-Initio Modelling 11/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models An estimate on the problem’s size. The Universe is not enough A search volume of 2000 dummy atoms has 2 2000 ≈ 10 600 possible conformations, i.e. scattering curves. On 40.000.000 conformations per hour per CPU, 1000 CPUs, 24 hours a day, 365 days a year one would spend the next couple of universes’ time on enumerating all scattering curves! Daniel Franke — Ab-Initio Modelling 12/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models Imposing restrictions in solution space. A valid conformation is ... connected: particle beads must be interconnected tightly packed: particle beads shall be tightly packed, avoid loose strands centered: assemble the particle within the search volume, avoid boundary contact in right shape: oblate or prolate shapes can be enforced Daniel Franke — Ab-Initio Modelling 13/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models Advances And Differences In Programs Selection Scheme DAMMIN DAMMIF At the current iteration: dark blue particle, might become solvent light blue solvent, might become particle white solvent, won’t change Daniel Franke — Ab-Initio Modelling 14/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models D AMMIF Walkthrough $> dammif shape.out Daniel Franke — Ab-Initio Modelling 15/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models D AMMIF Output Reading the output of D AMMIF Step: 1, T: 0.130E-03, 42/1941, Succ: 1229, Eval: 20001, CPU: 00:00:03 Rf: 0.0875, Los: 0.17, Dis: 0.00, Rg: 0.15, Cen:22.57, Ani: 0.00, Fit: 0.0989 Step Step number T Temperature, artifical p/a Number of particle beads of all beads Succ Number of successfull iterations at current T Eval Accumulated number of iterations CPU Accumulated runtime Daniel Franke — Ab-Initio Modelling 16/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models D AMMIF Output Reading the output of D AMMIF (cont.) Step: 1, T: 0.130E-03, 42/1941, Succ: 1229, Eval: 20001, CPU: 00:00:03 Rf: 0.0875, Los: 0.17, Dis: 0.00, Rg: 0.15, Cen:22.57, Ani: 0.00, Fit: 0.0989 Rf Goodness of Fit, data only Los Contribution of Looseness Penalty Dis Contribution of Disconnectivity Penalty Per Contribution of Periphal Penalty Ani Contribution of Anisometry Penalty Fit Goodness of Fit, data and penalties Daniel Franke — Ab-Initio Modelling 17/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models Outline Introduction 1 Ab-Initio Modelling 2 3 Obtaining Models Postprocessing Models 4 Daniel Franke — Ab-Initio Modelling 18/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models Sequentially on your local machine Windows; .bat files dammif lyz.out --mode=slow --prefix FMRP1 dammif lyz.out --mode=slow --prefix FMRP2 dammif lyz.out --mode=slow --prefix FMRP3 dammif lyz.out --mode=slow --prefix FMRP4 dammif lyz.out --mode=slow --prefix FMRP5 dammif lyz.out --mode=slow --prefix FMRP6 dammif lyz.out --mode=slow --prefix FMRP7 dammif lyz.out --mode=slow --prefix FMRP8 dammif lyz.out --mode=slow --prefix FMRP9 dammif lyz.out --mode=slow --prefix FMRP10 Daniel Franke — Ab-Initio Modelling 19/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models Sequentially on your local machine Linux, MacOS; bash syntax for i in ‘seq 1 10‘ ; do dammif --prefix=lyz-\$i --mode=slow lyz.out; done Daniel Franke — Ab-Initio Modelling 20/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models In parallel on your local cluster Please contact your system administrator for details of your cluster and how to submit jobs. Important: as processes are being run in parallel, multiple may be started at the same time – with the same random seed – resulting in exactly the same model. Make sure to redefine the random seed for each run! Daniel Franke — Ab-Initio Modelling 21/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models Input redirection Fine tuning parameters in scripts 1 Start dammif in slow mode once, abort 2 Find the $prefix.in file 3 Modify as needed 4 Run dammif as $> dammif --prefix=... --mode=i < modified.in Daniel Franke — Ab-Initio Modelling 22/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models In parallel using ATSAS-Online http://www.embl-hamburg.de/biosaxs/atsas-online/ Create an account (email address only) and submit your dammin/dammif jobs to the EMBL BioSAXS cluster. Daniel Franke — Ab-Initio Modelling 23/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models In parallel on the GRID http://www.wenmr.org/wenmr/ab-initio-modelling In preparation and not yet available. A worldwide e-Infrastructure for NMR and structural biology. Daniel Franke — Ab-Initio Modelling 24/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models Outline Introduction 1 Ab-Initio Modelling 2 3 Obtaining Models Postprocessing Models 4 Daniel Franke — Ab-Initio Modelling 25/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models Postprocessing Models How to proceed ... With multiple models: find those that are most similar (uniqueness of reconstruction is not guaranteed) OR group models into clusters superimpose and average the selection restart fitting process using the averaged model Daniel Franke — Ab-Initio Modelling 26/35
Introduction Ab-Initio Modelling Obtaining Models Postprocessing Models Multiple models Funari et al. (2000) J. Biol. Chem. 275, 31283–31288. 5S RNA, multiple solutions with equally good fit. Daniel Franke — Ab-Initio Modelling 27/35
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