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Generate the most probable trajectory between two states

Your email adress: (Recommended, for notification)


Job title: (Only alphanumerical characters)


PDB file of initial state (Maximum is 1000 atoms)
CA only for proteins, 3 atoms per residue for nucleic acids
Ex: 1ANF_ca.pdb


PDB file of final state (Maximum is 1000 atoms)
The program will first superpose (i.e. run Profit) the 2 structures (CA only for proteins). The two PDB files (initial and final) should have EXACTLY the same number of atoms.
Ex: 1OMP_ca.pdb


Length of the simulation (typically 100-200, in arbitrary units)

Time step for each snapshot along the path

Cutoff value for the ENM (default is 10 Angstrom)

Delta_E between the 2 states = E_start - E_final (in kcal/Mol)
See Figure below on the left for illustration

Elastic constant (left and right) in kcal/mol/Angstr**2
See Figure below on the right for illustration
A rule of thumb is that k*(cutoff)**2 # 10 kcal/Mol, within a factor of 2.
k_left k_right




Input data formats

  • The job title is just for your own identification, but note that it will show up in the public job queue (but your results will not be public).

  • The coordinate files should be in PDB format, with only a single structure (no multiple models). Only CA atoms are accepted as this stage for proteins; the limit is 1000 residues. A selection of 3-4 atoms should be used for nucleic acids.

    The two files MUST have the same number of (CA) atoms; here they will be structurally aligned internally by Profit.

  • The number of states is the length of the simulation divided by the time step. It should be of the order of 100.
  • The length of the simulation T should be such that the total action Stot in the log file does not change very much if T is increased (i.e. the user should check that the asymptotic regime has been reached).

Output

  • In addition to the trajectory in Pymol format, the coordinates of the transition state are given, as well as the total action Stot and the energy of the transition state U_L (measured with respect to the energy of the left -initial- state).
  • a Q1 vs Q2 plot will also be produced in postscript format, where Q1 is the number of contacts as in the initial state, and Q2 the number of contacts as in the final state, for each point along the trajectory.
    Here is an example (adenylate kinase), where the trajectory obtained with UMMS is also presented.
  • If needed, a Q1-specific - Q2-specific vs Q-common plot can also be built, upon request. This kind of plot reveals possible unfolding during the transition (see Okasaki et al., 2006).
  • The Elastic Energy during the transition can be calculated. The attached plot demonstrates that MinActionPath generates a trajectory with less elastic energy than UMMS linearly interpolated one (see curve pink+green vs blue+red curve).
    This again concernes adenylate kinase with elastic spring constants of 0.1 kcal/Mol/Angstr^2 for both sides.
  • Finally, the question of the robustness of the trajectory with respect of the k1/k2 ratio, i.e. the elastic constants for both sides of the reaction, is of interest. Here is a Q1 vs Q2 plot for adenylate kinase and k2/k1=5, k1=k2 and k1/k2=2.




  Marc Delarue http://lorentz.dynstr.pasteur.fr
Page last modified 11:52 March 03, 2015.