Source code for MDAnalysis.analysis.contacts

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"""
Native contacts analysis --- :mod:`MDAnalysis.analysis.contacts`
================================================================

This module contains classes to analyze native contacts *Q* over a
trajectory. Native contacts of a conformation are contacts that exist
in a reference structure and in the conformation. Contacts in the
reference structure are always defined as being closer than a distance
`radius`. The fraction of native contacts for a conformation can be
calculated in different ways. This module supports 3 different metrics
listed below, as well as custom metrics.

1. *Hard Cut*: To count as a contact the atoms *i* and *j* have to be at least
   as close as in the reference structure.

2. *Soft Cut*: The atom pair *i* and *j* is assigned based on a soft potential
   that is 1 if the distance is 0, 1/2 if the distance is the same as in
   the reference and 0 for large distances. For the exact definition of the
   potential and parameters have a look at function :func:`soft_cut_q`.

3. *Radius Cut*: To count as a contact the atoms *i* and *j* cannot be further
   apart than some distance `radius`.

The "fraction of native contacts" *Q(t)* is a number between 0 and 1 and
calculated as the total number of native contacts for a given time frame
divided by the total number of contacts in the reference structure.


Examples for contact analysis
-----------------------------

One-dimensional contact analysis
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

As an example we analyze the opening ("unzipping") of salt bridges
when the AdK enzyme opens up; this is one of the example trajectories
in MDAnalysis. ::

    import numpy as np
    import matplotlib.pyplot as plt
    import MDAnalysis as mda
    from MDAnalysis.analysis import contacts
    from MDAnalysis.tests.datafiles import PSF,DCD
    # example trajectory (transition of AdK from closed to open)
    u = mda.Universe(PSF,DCD)
    # crude definition of salt bridges as contacts between NH/NZ in ARG/LYS and
    # OE*/OD* in ASP/GLU. You might want to think a little bit harder about the
    # problem before using this for real work.
    sel_basic = "(resname ARG LYS) and (name NH* NZ)"
    sel_acidic = "(resname ASP GLU) and (name OE* OD*)"
    # reference groups (first frame of the trajectory, but you could also use a
    # separate PDB, eg crystal structure)
    acidic = u.select_atoms(sel_acidic)
    basic = u.select_atoms(sel_basic)
    # set up analysis of native contacts ("salt bridges"); salt bridges have a
    # distance <6 A
    ca1 = contacts.Contacts(u, select=(sel_acidic, sel_basic),
                            refgroup=(acidic, basic), radius=6.0)
    # iterate through trajectory and perform analysis of "native contacts" Q
    ca1.run()
    # print number of averave contacts
    average_contacts = np.mean(ca1.results.timeseries[:, 1])
    print('average contacts = {}'.format(average_contacts))
    # plot time series q(t)
    fig, ax = plt.subplots()
    ax.plot(ca1.results.timeseries[:, 0], ca1.results.timeseries[:, 1])
    ax.set(xlabel='frame', ylabel='fraction of native contacts',
           title='Native Contacts, average = {:.2f}'.format(average_contacts))
    fig.show()


The first graph shows that when AdK opens, about 20% of the salt
bridges that existed in the closed state disappear when the enzyme
opens. They open in a step-wise fashion (made more clear by the movie
`AdK_zipper_cartoon.avi`_).

.. _`AdK_zipper_cartoon.avi`:
   http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803350/bin/NIHMS150766-supplement-03.avi

.. rubric:: Notes

Suggested cutoff distances for different simulations

* For all-atom simulations, cutoff = 4.5 Å
* For coarse-grained simulations, cutoff = 6.0 Å


Two-dimensional contact analysis (q1-q2)
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Analyze a single DIMS transition of AdK between its closed and open
conformation and plot the trajectory projected on q1-q2
:footcite:p:`Franklin2007` ::


    import MDAnalysis as mda
    from MDAnalysis.analysis import contacts
    from MDAnalysisTests.datafiles import PSF, DCD
    u = mda.Universe(PSF, DCD)
    q1q2 = contacts.q1q2(u, 'name CA', radius=8)
    q1q2.run()

    f, ax = plt.subplots(1, 2, figsize=plt.figaspect(0.5))
    ax[0].plot(q1q2.results.timeseries[:, 0], q1q2.results.timeseries[:, 1],
               label='q1')
    ax[0].plot(q1q2.results.timeseries[:, 0], q1q2.results.timeseries[:, 2],
               label='q2')
    ax[0].legend(loc='best')
    ax[1].plot(q1q2.results.timeseries[:, 1],
               q1q2.results.timeseries[:, 2], '.-')
    f.show()

Compare the resulting pathway to the `MinActionPath result for AdK`_
:footcite:p:`Franklin2007`.

.. _MinActionPath result for AdK:
   http://lorentz.dynstr.pasteur.fr/joel/adenylate.php


Writing your own contact analysis
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

The :class:`Contacts` class has been designed to be extensible for your own
analysis. As an example we will analyze when the acidic and basic groups of AdK
are in contact which each other; this means that at least one of the contacts
formed in the reference is closer than 2.5 Å.

For this we define a new function to determine if any contact is closer than
2.5 Å; this function must implement the API prescribed by :class:`Contacts`::

    def is_any_closer(r, r0, dist=2.5):
        return np.any(r < dist)

The first two parameters `r` and `r0` are provided by :class:`Contacts` when it
calls :func:`is_any_closer` while the others can be passed as keyword args
using the `kwargs` parameter in :class:`Contacts`.

Next we are creating an instance of the :class:`Contacts` class and use the
:func:`is_any_closer` function as an argument to `method` and run the analysis::

    # crude definition of salt bridges as contacts between NH/NZ in ARG/LYS and
    # OE*/OD* in ASP/GLU. You might want to think a little bit harder about the
    # problem before using this for real work.
    sel_basic = "(resname ARG LYS) and (name NH* NZ)"
    sel_acidic = "(resname ASP GLU) and (name OE* OD*)"

    # reference groups (first frame of the trajectory, but you could also use a
    # separate PDB, eg crystal structure)
    acidic = u.select_atoms(sel_acidic)
    basic = u.select_atoms(sel_basic)

    nc = contacts.Contacts(u, select=(sel_acidic, sel_basic),
                           method=is_any_closer,
                           refgroup=(acidic, basic), kwargs={'dist': 2.5})
    nc.run()

    bound = nc.results.timeseries[:, 1]
    frames = nc.results.timeseries[:, 0]

    f, ax = plt.subplots()

    ax.plot(frames, bound, '.')
    ax.set(xlabel='frame', ylabel='is Bound',
           ylim=(-0.1, 1.1))

    f.show()


Functions
---------

.. autofunction:: hard_cut_q
.. autofunction:: soft_cut_q
.. autofunction:: radius_cut_q
.. autofunction:: contact_matrix
.. autofunction:: q1q2

Classes
-------

.. autoclass:: Contacts
   :members:

.. rubric:: References
.. footbibliography::

"""
import os
import errno
import warnings
import bz2
import functools

import numpy as np

import logging

import MDAnalysis
import MDAnalysis.lib.distances
from MDAnalysis.lib.util import openany
from MDAnalysis.analysis.distances import distance_array
from MDAnalysis.core.groups import AtomGroup, UpdatingAtomGroup
from .base import AnalysisBase

logger = logging.getLogger("MDAnalysis.analysis.contacts")


[docs] def soft_cut_q(r, r0, beta=5.0, lambda_constant=1.8): r"""Calculate fraction of native contacts *Q* for a soft cut off The native contact function is defined as :footcite:p:`Best2013` .. math:: Q(r, r_0) = \frac{1}{1 + e^{\beta (r - \lambda r_0)}} Reasonable values for different simulation types are - *All Atom*: `lambda_constant = 1.8` (unitless) - *Coarse Grained*: `lambda_constant = 1.5` (unitless) Parameters ---------- r: array Contact distances at time t r0: array Contact distances at time t=0, reference distances beta: float (default 5.0 Angstrom) Softness of the switching function lambda_constant: float (default 1.8, unitless) Reference distance tolerance Returns ------- Q : float fraction of native contacts """ r = np.asarray(r) r0 = np.asarray(r0) result = 1/(1 + np.exp(beta*(r - lambda_constant * r0))) return result.sum() / len(r0)
[docs] def hard_cut_q(r, cutoff): """Calculate fraction of native contacts *Q* for a hard cut off. The cutoff can either be a float or a :class:`~numpy.ndarray` of the same shape as `r`. Parameters ---------- r : ndarray distance matrix cutoff : ndarray | float cut off value to count distances. Can either be a float of a ndarray of the same size as distances Returns ------- Q : float fraction of contacts """ r = np.asarray(r) cutoff = np.asarray(cutoff) y = r <= cutoff return y.sum() / r.size
[docs] def radius_cut_q(r, r0, radius): """calculate native contacts *Q* based on the single distance radius. Parameters ---------- r : ndarray distance array between atoms r0 : ndarray unused to fullfill :class:`Contacts` API radius : float Distance between atoms at which a contact is formed Returns ------- Q : float fraction of contacts """ return hard_cut_q(r, radius)
[docs] def contact_matrix(d, radius, out=None): """calculate contacts from distance matrix Parameters ---------- d : array-like distance matrix radius : float distance below which a contact is formed. out : array (optional) If `out` is supplied as a pre-allocated array of the correct shape then it is filled instead of allocating a new one in order to increase performance. Returns ------- contacts : ndarray boolean array of formed contacts """ if out is not None: out[:] = d <= radius else: out = d <= radius return out
[docs] class Contacts(AnalysisBase): """Calculate contacts based observables. The standard methods used in this class calculate the fraction of native contacts *Q* from a trajectory. .. rubric:: Contact API By defining your own method it is possible to calculate other observables that only depend on the distances and a possible reference distance. The **Contact API** prescribes that this method must be a function with call signature ``func(r, r0, **kwargs)`` and must be provided in the keyword argument `method`. Attributes ---------- results.timeseries : numpy.ndarray 2D array containing *Q* for all refgroup pairs and analyzed frames timeseries : numpy.ndarray Alias to the :attr:`results.timeseries` attribute. .. deprecated:: 2.0.0 Will be removed in MDAnalysis 3.0.0. Please use :attr:`results.timeseries` instead. .. versionchanged:: 1.0.0 ``save()`` method has been removed. Use ``np.savetxt()`` on :attr:`Contacts.results.timeseries` instead. .. versionchanged:: 1.0.0 added ``pbc`` attribute to calculate distances using PBC. .. versionchanged:: 2.0.0 :attr:`timeseries` results are now stored in a :class:`MDAnalysis.analysis.base.Results` instance. .. versionchanged:: 2.2.0 :class:`Contacts` accepts both AtomGroup and string for `select` """ def __init__(self, u, select, refgroup, method="hard_cut", radius=4.5, pbc=True, kwargs=None, **basekwargs): """ Parameters ---------- u : Universe trajectory select : tuple(AtomGroup, AtomGroup) | tuple(string, string) two contacting groups that change over time refgroup : tuple(AtomGroup, AtomGroup) two contacting atomgroups in their reference conformation. This can also be a list of tuples containing different atom groups radius : float, optional (4.5 Angstroms) radius within which contacts exist in refgroup method : string | callable (optional) Can either be one of ``['hard_cut' , 'soft_cut', 'radius_cut']`` or a callable with call signature ``func(r, r0, **kwargs)`` (the "Contacts API"). pbc : bool (optional) Uses periodic boundary conditions to calculate distances if set to ``True``; the default is ``True``. kwargs : dict, optional dictionary of additional kwargs passed to `method`. Check respective functions for reasonable values. verbose : bool (optional) Show detailed progress of the calculation if set to ``True``; the default is ``False``. Attributes ---------- n_initial_contacts : int Total number of initial contacts. r0 : list[numpy.ndarray] List of distance arrays between reference groups. Notes ----- .. versionchanged:: 1.0.0 Changed `selection` keyword to `select` """ self.u = u super(Contacts, self).__init__(self.u.trajectory, **basekwargs) self.fraction_kwargs = kwargs if kwargs is not None else {} if method == 'hard_cut': self.fraction_contacts = hard_cut_q elif method == 'soft_cut': self.fraction_contacts = soft_cut_q elif method == 'radius_cut': self.fraction_contacts = functools.partial(radius_cut_q, radius=radius) else: if not callable(method): raise ValueError("method has to be callable") self.fraction_contacts = method self.select = select self.grA, self.grB = (self._get_atomgroup(u, sel) for sel in select) self.pbc = pbc # contacts formed in reference self.r0 = [] self.initial_contacts = [] #get dimension of box if pbc set to True if self.pbc: self._get_box = lambda ts: ts.dimensions else: self._get_box = lambda ts: None if isinstance(refgroup[0], AtomGroup): refA, refB = refgroup self.r0.append(distance_array(refA.positions, refB.positions, box=self._get_box(refA.universe))) self.initial_contacts.append(contact_matrix(self.r0[-1], radius)) else: for refA, refB in refgroup: self.r0.append(distance_array(refA.positions, refB.positions, box=self._get_box(refA.universe))) self.initial_contacts.append(contact_matrix(self.r0[-1], radius)) self.n_initial_contacts = self.initial_contacts[0].sum() @staticmethod def _get_atomgroup(u, sel): select_error_message = ("selection must be either string or a " "static AtomGroup. Updating AtomGroups " "are not supported.") if isinstance(sel, str): return u.select_atoms(sel) elif isinstance(sel, AtomGroup): if isinstance(sel, UpdatingAtomGroup): raise TypeError(select_error_message) else: return sel else: raise TypeError(select_error_message) def _prepare(self): self.results.timeseries = np.empty((self.n_frames, len(self.r0)+1)) def _single_frame(self): self.results.timeseries[self._frame_index][0] = self._ts.frame # compute distance array for a frame d = distance_array(self.grA.positions, self.grB.positions, box=self._get_box(self._ts)) for i, (initial_contacts, r0) in enumerate(zip(self.initial_contacts, self.r0), 1): # select only the contacts that were formed in the reference state r = d[initial_contacts] r0 = r0[initial_contacts] q = self.fraction_contacts(r, r0, **self.fraction_kwargs) self.results.timeseries[self._frame_index][i] = q @property def timeseries(self): wmsg = ("The `timeseries` attribute was deprecated in MDAnalysis " "2.0.0 and will be removed in MDAnalysis 3.0.0. Please use " "`results.timeseries` instead") warnings.warn(wmsg, DeprecationWarning) return self.results.timeseries
def _new_selections(u_orig, selections, frame): """create stand alone AGs from selections at frame""" u = MDAnalysis.Universe(u_orig.filename, u_orig.trajectory.filename) u.trajectory[frame] return [u.select_atoms(s) for s in selections]
[docs] def q1q2(u, select='all', radius=4.5): """Perform a q1-q2 analysis. Compares native contacts between the starting structure and final structure of a trajectory :footcite:p:`Franklin2007`. Parameters ---------- u : Universe Universe with a trajectory select : string, optional atoms to do analysis on radius : float, optional distance at which contact is formed Returns ------- contacts : :class:`Contacts` Contact Analysis that is set up for a q1-q2 analysis .. versionchanged:: 1.0.0 Changed `selection` keyword to `select` Support for setting ``start``, ``stop``, and ``step`` has been removed. These should now be directly passed to :meth:`Contacts.run`. """ selection = (select, select) first_frame_refs = _new_selections(u, selection, 0) last_frame_refs = _new_selections(u, selection, -1) return Contacts(u, selection, (first_frame_refs, last_frame_refs), radius=radius, method='radius_cut')