Copyright 2014-2020 by Evgueni Kovriguine

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2D NMR line shapes: IDAP models in TITAN

 

In this module, the two-dimensional line shape models are developed for use with TITAN [1]. TITAN was developed by Chris Waudby and described in [Waudby, C. A., A. Ramos, L. D. Cabrita and J. Christodoulou (2016). "Two-dimensional NMR lineshape analysis." Scientific Reports 6: 8]. You can obtain TITAN from  http://www.nmr-titan.com.

The kinetic matrices for these models were developed  in Mathematical Models

 


    Contents

 

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    Introduction

 

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    Models

 

 

Simple two-state models

Isomerization coupled with ligand binding

--- Models to be added --------

Dimerization coupled with ligand binding

 

 


    Developer's notes

 

  1. All IDAP models use K_A instead of log10(K_A). Log was used originally in IDAP to allow for a more uniform Monte-Carlo sampling of starting parameters. However, this has not worked well . Use of K_A is aligned with the LineShapeKin Simulation conventions.
  2. I am setting all concentration units to mol/L. This means that input values for the Rtotal and Ltotal will have to be scaled when comparing to original TITAN models utilizing TITAN sample data.
  3. IDAP thermodynamic equation solvers cannot deal with ligand concentration equal to zero. Set the ligand-free point to a very small value: 1e-9 or 1e-6
  4. The TITAN_IDAP_interface is a class to derive all models for TITAN from. TITAN_IDAP_interface adds output of the populations and also checks for the zeros in L concentration array.
  5. Original TITAN models may be used using IDAP-TITAN control scripts if their parent class is changed to TITAN_IDAP_interface.
  6. It is possible to include IDAP models to TITAN GUI:

    1. copy setup_binding_model.m from the titan/ folder to your working folder.

    2. insert references to necessary IDAP models in bm_list in setup_binding_model() function. Example:
      bm_list = {
      line_shape_2D_TITAN.U_R_RL
      bmNoExchange
      bmTwoState
      ...

    3. When you start TITAN in that folder, and it will use your edited setup_binding_model.m instead of the original one from titan/.

    Warning about the units in the original TITAN models

    TITAN operates with all concentrations in micromoles per L. This would not have effect on populations as the equilibrium constant is also supplied in micromolar units. However, kinetic matrices are calculated using equilbrium concentration of [L] and that comes out in micromoles from the calculations! This may be a problem in some cases!

    PSEUDOFIRST-ORDER RATE CONSTANT IS OK: I checked the two-state model. The kon is derived as koff/Kd. It will be 1000x smaller than it should be. However, when calculating the kab we multiply kon by Lfree, which is 1000 larger because of the micromolar units. Therefore, there is compensation of effect of the units in the original TITAN models (at least in bmTwoState.m).

     


Steps for adapting IDAP model for use in TITAN

    1. take a model from line_shape_2D_TITAN/ with necessary number of states as a template
    2. Manually insert number of states and number constants in the Properties section
    3. Insert thermodynamic calculation
    4. Insert kinetic matrix
    5. make sure population vector is called p0 and transposed to a column.
    6. Normalize it by Rtotal
    7. Implement vectorized population calculations for vectorized equilbirium thermodynamic models (check in Mathematical_models/Equilibrium_thermodynamic_models/index.htm)
    8. Test calculations using HSQC mode vs LineShapeKin Simulation and vs TITAN where possible.

 

 

 

To do: The control scripts for data fitting

 

 

 

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