sspre

sspre contains functions related to paramagnetic relaxation enhancement (PRE) analysis of IDPs.

SSPRE is a class that takes a SSProtein objecs and can perform PRE-related calculations.

This is, in many ways, a purely functional class, but given it’s very specific goal it is separated out into its own class in the interest of more robust modularity.

There are a number of internal functions, but the only public facing function is the generate_PRE_profile function below. This gives both the intensity ratio profile and the transverse relaxation rate (Gamma_2) profiles. For more detail on the calculation of these profiles see the help associated with generate_PRE_profile function

For more information on caculation of PREs using method see the Supplementary information in the following two papers.

Meng, W., Lyle, N., Luan, B., Raleigh, D.P., and Pappu, R.V. (2013). Experiments and simulations show how long-range contacts can form in expanded unfolded proteins with negligible secondary structure. Proc. Natl. Acad. Sci. U. S. A. 110, 2123-2128.

Das, R.K., Huang, Y., Phillips, A.H., Kriwacki, R.W., and Pappu, R.V. (2016). Cryptic sequence features within the disordered protein p27Kip1 regulate cell cycle signaling. Proc. Natl. Acad. Sci. U. S. A. 113, 5616- 5621.

Peran, I., Holehouse, A. S., Carrico, I. S., Pappu, R. V., Bilsel, O., & Raleigh, D. P. (2019). Unfolded states under folding conditions accommodate sequence-specific conformational preferences with random coil-like dimensions. Proceedings of the National Academy of Sciences of the United States of America, 116(25), 12301–12310.

class soursop.sspre.SSPRE(SSProteinObject, tau_c, t_delay, R_2D, W_H)[source]

Class for generating synthetic paramagnetic resonance enhancement profiles.

__init__(SSProteinObject, tau_c, t_delay, R_2D, W_H)[source]

Initialization function for creating a SSPRE object. The resulting object can then be used to calculate PRE profiles from the underlying ensemble. This calculation is extremely fast.

Parameters:

SSProteinObject (SSProtein-derived object) – SSProtein object extracted from a SSTrajectory objected. The SSProtein object is the main object that most protein-based analysis is performed over in SOURSOP.
tau_c (float) – tau_c is the effective correlation time, measured in nanoseconds, which is typically between 1 and 30.
t_delay (float) – Total duration of the INEPT delays from the PRE experiment, as measured in ms. This will depend on the pulse sequence used, but is typically around 1-30 ms for HSQC.
R_2D (float) – Is the transverse relaxation rate of the backbone amide protons in the diamagnetic form of the protein, measured in Herz (i.e. ‘per second’). A value of around 10 might be expected.
W_H (float) – Is the proton Larmor frequency, which is typically the “MHz” value associated with the magnet, given in Hz. For examle, a 600 MHz magnet would use the value 600000000. Note that the proton Larmor frequency at 1 Tesla = 267530000 per second per Tesla.

generate_PRE_profile(label_position, spin_label_atom='CB', target_relaxation_atom='N')[source]

Construct a PRE intensity profile and gamma profile based on a nitroxide spin label being placed at the label position position on the $spin_label_atom atom. By default this is the CB and the PRE distance to be used to asses relaxation comes from the CB-backbone N distances (as used in work by Meng & Lyle [1], Das [2], and Peran & Holehouse [3]).

The PRE profile describes the intensity ratio (I_paramagnetic / I_diamagnetic), and typically varies between 0 and 1. When the intensity ratio ~0 the spin label dominantes relaxation and suggests the residue in question is near the spin label. When the intensity ratio is ~1 the relaxation is primarily through non-spin label mediated mechanisms suggesting the label and the residue are far apart.

The gamma profile describes the spin-label induced amide proton relaxation rate in units of per-second, providing another observable that can be directly compared with experiment.

This function is extremely fast (sub 10 seconds on a ~6000 frame ensemble).

Parameters:

label_position (int) – Position in the sequence at which the spin-label is located. Should ideally contain a CB atom (i.e. not be be glycine), else the label atom must be set to ‘CA’ see below.
spin_label_atom (str (default = 'CB')) – Name of the atom upon which the spin label is located. Should really be CB but may be changed if a residue lacks a CB atom (e.g. a glycine is in the place of the Cys nitroxide spin labeled residue).
target_relaxation_atom (str (default='N')) – Name of the atom where relaxation is being performed. This should be ‘N’ (backbone amide) as that’s how this approach is parameterized - highly recommended that this isn’t changed. If it is changed the method will look for an atom of this name in every residue. Again, it is STRONGLY recommended this isn’t changed.

Returns:

Returns a 2 place tuple - tuple position 0 is the PRE intensity profile and tuple position 1 is the PRE H1 relaxatation profile.

Return type:

tuple

References

[1] Meng, W., Lyle, N., Luan, B., Raleigh, D.P., and Pappu, R.V. (2013). Experiments and simulations show how long-range contacts can form in expanded unfolded proteins with negligible secondary structure. Proc. Natl. Acad. Sci. U. S. A. 110, 2123-2128.

[2] Das, R.K., Huang, Y., Phillips, A.H., Kriwacki, R.W., and Pappu, R.V. (2016). Cryptic sequence features within the disordered protein p27Kip1 regulate cell cycle signaling. Proc. Natl. Acad. Sci. U. S. A. 113, 5616- 5621.

[3] Peran, I., Holehouse, A. S., Carrico, I. S., Pappu, R. V., Bilsel, O., & Raleigh, D. P. (2019). Unfolded states under folding conditions accommodate sequence-specific conformational preferences with random coil-like dimensions. Proceedings of the National Academy of Sciences of the United States of America, 116(25), 12301–12310.