ProDy¶

9/29/2022¶

Original slides courtesy Ahmet Bakan

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ProDy stands for Protein Dynamics,

  • an API that is very suitable for interactive usage
  • comes with several command line applications

ProDy is designed for normal mode analysis, but also is

  • a powerful tool for handling macromolecular structures
  • useful for analysis of molecular dynamics trajectories
  • useful for sequence conservation and coevolution analysis (Evol)

This lecture contains:

  • an into to some ProDy conventions
  • handling protein structure files
  • an intro to some dynamics calculations
  • some ProDy design principles

Import from ProDy¶

In interactive sessions, the following is safe (no name conflicts)

In [3]:
from prody import *
checkUpdates()

When developing software, prefer importing specific functions/classes or prefixing

In [4]:
import prody as pd
from prody import parsePDB

ProDy API naming conventions¶

Function names¶

ProDy functions start with an action verb followed by one or more names or an abbreviation/extension, i.e. doSomething:

  • parseEXT(): parse a file in EXT format, e.g. parsePDB, parseDCD
  • writeEXT(): write a file in EXT format, e.g. writePDB, writeDCD
  • fetchSTH(): download a file, e.g. fetchPDB, fetchMSA
  • calcSTH(): calculate something, e.g. calcRMSD, calcGyradius, calcANM
  • showSTH(): show a plotting of something, e.g. showCrossCorrelations, showProtein
  • saveSTH(): save a ProDy object instance to disk, e.g. saveAtoms
  • loadSTH(): save a ProDy object instance to disk, e.g. loadAtoms

Class names¶

Class names start with upper case letters and are abbreviations or words in camel case style, e.g. AtomGroup, Selection, ANM, etc.

Class method names¶

Class method naming is similar to function naming:

  • Class.numSomething: return number of the thing, e.g. AtomGroup.numAtoms returns number of atoms
  • Class.getSomething: return an attribute, e.g. AtomGroup.getNames returns atom names
  • Class.setSomething: set/update an attribute, e.g. AtomGroup.setNames sets atom names
  • Class.buildMatrix: builds a matrix, e.g. PCA.buildCovariance calculates covariance matrix

Usage example¶

In [5]:
ubi = parsePDB('1ubi')
In [6]:
ubi
Out[6]:
<AtomGroup: 1ubi (683 atoms)>

TIP: to see a list of available functions, just type the action word (calc, show, get, etc.), and use TAB completion.

In [7]:
ubi.numAtoms()
Out[7]:
683
In [8]:
calcGyradius(ubi)
Out[8]:
12.085104173005442

Visualization¶

In [9]:
%matplotlib inline
showProtein(ubi)

/home/anupam06/anaconda3/lib/python3.9/site-packages/prody/proteins/functions.py:265: MatplotlibDeprecationWarning: Axes3D(fig) adding itself to the figure is deprecated since 3.4. Pass the keyword argument auto_add_to_figure=False and use fig.add_axes(ax) to suppress this warning. The default value of auto_add_to_figure will change to False in mpl3.5 and True values will no longer work in 3.6.  This is consistent with other Axes classes.
  show = Axes3D(cf)
Out[9]:
<Axes3D:xlabel='x', ylabel='y'>

Better Visualization¶

In [10]:
import py3Dmol
showProtein(ubi)

You appear to be running in JupyterLab (or JavaScript failed to load for some other reason). You need to install the 3dmol extension:
jupyter labextension install jupyterlab_3dmol

Out[10]:
<py3Dmol.view at 0x7f4561276ca0>
In [11]:
%%html
<div id="atomcnt" style="width: 500px"></div>
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File handling¶

ProDy has a custom format for directly saving atom groups.

In [12]:
saveAtoms(ubi)
Out[12]:
'1ubi.ag.npz'

Can also read/write standard protein formats (PDB,PQR)

In [13]:
writePDB('ubi.pdb', ubi)
Out[13]:
'ubi.pdb'
In [14]:
parsePDB(writePDB('ubi.pdb', ubi))
Out[14]:
<AtomGroup: ubi (683 atoms)>

Structures and AtomGroups¶

Protein Data Bank (PDB) Structure files can be parsed using parsePDB. For a given PDB identifier, this function will download the file if needed.

In [15]:
ag = parsePDB('1vrt')

Structure data parsed from the file is stored in an AtomGroup instance:

In [16]:
type(ag)
Out[16]:
prody.atomic.atomgroup.AtomGroup

Why AtomGroup?

  • not Molecule, because structures are usually made up from multiple molecules
  • not Structure, because PDB format is sometimes used for storing small-molecules

AtomGroup made sense for handling bunch of atoms, and is used by some other packages too.

Some AtomGroup methods¶

Check number of atoms and models (coordinate sets)

In [17]:
ag.numAtoms()
Out[17]:
7953
In [18]:
ag.numCoordsets()
Out[18]:
1

Getters¶

Use getSomething methods to access data parsed from the file

In [19]:
names = ag.getNames()
In [20]:
names
Out[20]:
array(['N', 'CA', 'C', ..., 'O', 'O', 'O'], dtype='<U6')
In [21]:
len(names)
Out[21]:
7953
In [22]:
print(names[0])

N
In [23]:
ag.getBetas()
Out[23]:
array([86.04, 85.23, 84.2 , ..., 64.55, 58.23, 46.98])

Note that get is followed by a plural name, and method returns a numpy array

Setters¶

Use setSomething methods to set attributes, but don't forget to pass an array or list with length equal to number of atoms

In [24]:
zeros = [0] * len(ag) # same as ag.numAtoms()
ag.setBetas(zeros)
In [25]:
ag.getBetas()
Out[25]:
array([0., 0., 0., ..., 0., 0., 0.])

Atom instances¶

You can get a handle for specific atoms by indexing

In [26]:
a0 = ag[0]
print(a0)

Atom N (index 0)

Note that getSomething and setSomething methods are available, but that thing is in singular form:

In [27]:
a0.getName()
Out[27]:
'N'
In [28]:
a0.getBeta() # we had just set it to zero
Out[28]:
0.0

Subset of atoms¶

Slicing an AtomGroup will return a handler called Selection for specified subset of atoms. Let's get every other atom:

In [29]:
eoa = ag[::2] # eoa: every other atom
print(eoa)

Selection 'index 0:7953:2'
In [30]:
print(len(eoa))
print(len(ag))

3977
7953

get and set methods in plural form are also available for Selection instances

In [31]:
eoa.getNames()
Out[31]:
array(['N', 'C', 'CB', ..., 'O', 'O', 'O'], dtype='<U6')

Hierarchical Views¶

Macromolecules have a hierarchical structure:

  • chain - a polypeptide or a nucleic acid chain
  • residue - an amino acid, nucleotide, small molecule, or an ion
  • atom - lowest level of hierarchy
  • segment - used by simulation programs and may be composed of multiple chains
In [32]:
ag.numChains()
Out[32]:
2
In [33]:
ag.numResidues()
Out[33]:
1233
In [34]:
showProtein(ag)

You appear to be running in JupyterLab (or JavaScript failed to load for some other reason). You need to install the 3dmol extension:
jupyter labextension install jupyterlab_3dmol

Out[34]:
<py3Dmol.view at 0x7f4560066f10>

Iterations¶

In [35]:
for ch in ag.iterChains():
    print('%s - %d residues' % (str(ch), ch.numResidues()))

Chain A - 688 residues
Chain B - 545 residues
In [36]:
for ch in ag.iterChains():
    print(ch)
    for res in ch:
        print(' |-%s' % res)
        break
    print('...')

Chain A
 |-PRO 4
...
Chain B
 |-ILE 5
...

Also iterAtoms (default), iterBonds, iterCoordsets, iterFragments, iterResidues, iterSegments

Indexing¶

Index with chain identifier to get a chain instance:

In [37]:
chA = ag['A']
print(chA)
type(chA)

Chain A
Out[37]:
prody.atomic.chain.Chain

Index with a pair of chain identifier and residue number to get a handle for a residue:

In [38]:
chA_res10 = ag['A', 10]
print(chA_res10)
type(chA_res10)

VAL 10
Out[38]:
prody.atomic.residue.Residue

Of course, plural forms of get and set methods and other methods are available:

In [39]:
chA_res10.getNames()
Out[39]:
array(['N', 'CA', 'C', 'O', 'CB', 'CG1', 'CG2'], dtype='<U6')
In [40]:
chA_res10.numAtoms()
Out[40]:
7
In [41]:
%%html
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Atom Selections¶

The atom selection engine is what makes ProDy a powerful tool. Selection grammar is similar to that of VMD but with added flexibility of Python. AtomGroup.select method accepts selection arguments and returns a Selection instance:

In [42]:
sel = ag.select('protein and name CA')
print(sel)
print('# of atoms: %d' % sel.numAtoms())
set(sel.getNames())

Selection 'protein and name CA'
# of atoms: 925
Out[42]:
{'CA'}

Same as using the keyword 'ca' or 'calpha'

In [43]:
ag.select('ca') == ag.select('calpha') == ag.select('protein and name CA')
Out[43]:
True

Selecting by distance¶

You can make proximity based selections:

In [44]:
kinase = parsePDB('3erk')
bindingsite = kinase.select('within 5 of (hetero and not water)')
print('# of atoms: %d' % bindingsite.numAtoms())
print(set(bindingsite.getResnames()))

# of atoms: 98
{'SB4', 'GLN', 'LEU', 'ASP', 'CYS', 'LYS', 'VAL', 'ILE', 'MET', 'SER', 'ALA', 'HOH'}

exwithin excludes the initial selection

In [45]:
noligand = kinase.select('exwithin 5 of (hetero and not water)')
print('# of atoms: %d' % noligand.numAtoms())
print(set(noligand.getResnames()))

# of atoms: 73
{'GLN', 'LEU', 'ASP', 'CYS', 'LYS', 'VAL', 'ILE', 'MET', 'SER', 'ALA', 'HOH'}
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Keyword arguments¶

Words used within the selection string that are not reserved keywords can be substituted with keyword arguments.

Select atoms that are close to a point in space:

In [47]:
import numpy as np
origin = np.zeros(3)
print(origin)
sel = ag.select('within 10 of origin', origin=origin)
sel

[0. 0. 0.]
Out[47]:
<Selection: 'index 3426 to 3437 3439 to 3461' from 1vrt (35 atoms)>
In [48]:
calcDistance(sel, origin)[:5]
Out[48]:
array([9.93856378, 9.16952812, 9.08634382, 9.79169985, 8.45576029])
In [49]:
ag.select('within 5 of center',center = calcCenter(ag))
Out[49]:
<Selection: 'index 4457 to 4...49 to 7353 7941' from 1vrt (19 atoms)>

Dot selection shorthand¶

Dot operator can also be used to make selections:

In [50]:
ag.calpha
Out[50]:
<Selection: 'calpha' from 1vrt (925 atoms)>
In [51]:
ag.name_CA_and_resname_ALA
Out[51]:
<Selection: 'name CA and resname ALA' from 1vrt (37 atoms)>

See full documentation of selection grammar at: http://prody.csb.pitt.edu/manual/reference/atomic/select.html

Coordinate Sets¶

AtomGroup can handle multiple models in a PDB file. Models are called coordinate sets.

In [52]:
ubi = parsePDB('2k39')
In [53]:
ubi.numCoordsets()
Out[53]:
116

Active coordinate set (ACS) can be queried or changed using getACSIndex and setACSIndex methods:

In [54]:
ubi.getACSIndex()
Out[54]:
0

Coordinates¶

Coordinates are numpy arrays

In [55]:
coords = ubi.getCoords()
coords.mean(axis=0)
Out[55]:
array([26.02865475, 25.60081316, 20.56833875])
In [56]:
ubi.setACSIndex(115)
ubi.getCoords().mean(axis=0)
Out[56]:
array([26.49875061, 26.09516897, 20.5057498 ])

Selections have their own active coordinate set indices:

In [57]:
ubi_ca = ubi.calpha
ubi_ca.getACSIndex()
Out[57]:
115
In [58]:
ubi_ca.setACSIndex(0)
print(ubi_ca.getACSIndex())
print(ubi.getACSIndex())

0
115

Operations with Atoms¶

Copying atoms¶

Call copy method to make a copy of AtomGroup or Selection instance

In [59]:
ag.copy()
Out[59]:
<AtomGroup: 1vrt (7953 atoms)>
In [60]:
ca = ag.select('ca')
ca.copy()
Out[60]:
<AtomGroup: 1vrt Selection 'ca' (925 atoms)>

AtomGroup addition¶

Lot's of customization has gone into ProDy classess handling atoms. Addition of AtomGoups (__add__) results in a new AtomGroup:

In [61]:
ag_copy = ag.copy()
moveAtoms(ag_copy, by=np.array([50, 50, 50]))
ag_copy['A'].setChid('C')
ag_copy['B'].setChid('D')
ag_new = ag + ag_copy
showProtein(ag_new)

You appear to be running in JupyterLab (or JavaScript failed to load for some other reason). You need to install the 3dmol extension:
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AtomGroup membership¶

You can use in to see whether a Selection is in another one (enabled by implementing Selection.__contains__() method):

In [62]:
ag.calpha in ag.backbone
Out[62]:
True
In [63]:
ag.backbone in ag.protein
Out[63]:
True
In [64]:
ag.water in ag.protein
Out[64]:
False
In [65]:
ag.water in ag
Out[65]:
True

Selection operations¶

You can use bitwise operations on selections as follows:

In [66]:
chA = ag.chain_A
chB = ag.chain_B
In [67]:
print(chA & chB) # intersection

None
In [68]:
sel = chA | chB # union
In [69]:
sel.getSelstr()
Out[69]:
'(chain A) or (chain B)'
In [70]:
~chA #not
Out[70]:
<Selection: 'not (chain A)' from 1vrt (3461 atoms)>

Store Data in AtomGroup¶

You can store arbitrary atomic data in AtomGroup class and make it persistent on disk:

In [71]:
atoms = parsePDB('1p38')
atoms.getResnums()
Out[71]:
array([  4,   4,   4, ..., 771, 773, 776])
In [72]:
resnum_fract = atoms.getResnums() / 10.
resnum_fract
Out[72]:
array([ 0.4,  0.4,  0.4, ..., 77.1, 77.3, 77.6])
In [73]:
atoms.setData('resnumfract', resnum_fract)
atoms.getData('resnumfract')
Out[73]:
array([ 0.4,  0.4,  0.4, ..., 77.1, 77.3, 77.6])

Saving to Files¶

In [74]:
saveAtoms(atoms)
Out[74]:
'1p38.ag.npz'
In [75]:
atoms = loadAtoms('1p38.ag.npz')
atoms.getData('resnumfract')
Out[75]:
array([ 0.4,  0.4,  0.4, ..., 77.1, 77.3, 77.6])

PDB Access¶

Fetch PDB files¶

Can request multiple files at once. Will download to local directory.

In [76]:
fetchPDB('1p38', '1r39', '@!~#') # searches working directory, local resources, then downloads
Out[76]:
['/home/anupam06/Documents/mmbios_workshop/day2/1p38.pdb.gz',
 '/home/anupam06/Documents/mmbios_workshop/day2/1r39.pdb.gz',
 None]
In [77]:
fetchPDBviaHTTP('1p38')
fetchPDBviaFTP('1p38')

Comparing and Aligning Structures¶

In [78]:
p38 = parsePDB('1p38')
bound = parsePDB('1zz2')
In [79]:
showProtein(p38, bound)

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jupyter labextension install jupyterlab_3dmol

Out[79]:
<py3Dmol.view at 0x7f45600d7e50>

Chain matching and RMSD¶

matchChains tries to match chains by sequence. Returns a list of all pairwise matches

In [80]:
apo_chA, bnd_chA, seqid, overlap = matchChains(p38, bound)[0]
print(bnd_chA)
print(seqid)
print(overlap)

AtomMap Chain A from 1zz2 -> Chain A from 1p38
99.5475113122172
92.08333333333333

Match is alpha carbon only

In [81]:
print(len(apo_chA),len(bnd_chA),len(p38),len(bound))

337 337 2962 2872
In [82]:
set(apo_chA.getNames())
Out[82]:
{'CA'}
In [83]:
calcRMSD(apo_chA, bnd_chA)
Out[83]:
72.93023086946586

Align chains¶

superpose(mobile, target)

  • Finds minimal RMSD pose of mobile with respect to target
In [84]:
bnd_chA, transformation = superpose(bnd_chA, apo_chA)
calcRMSD(bnd_chA, apo_chA)
Out[84]:
1.8628014908695485
In [85]:
showProtein(p38, bound)

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<py3Dmol.view at 0x7f4560090be0>

Building Biomolecules¶

PDB files often contain monomer coordinates, when the structure of the multimer can be obtained using symmetry operations. Let’s use some ProDy function to build tetrameric form of KcsA potassium channel:

In [86]:
# parse the monomer structure and PDB file header information
# the header includes transformations for forming tetramer
monomer, header = parsePDB('1k4c', header=True)
monomer
Out[86]:
<AtomGroup: 1k4c (4534 atoms)>
In [87]:
showProtein(monomer, legend=True)

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Out[87]:
<py3Dmol.view at 0x7f456119ca60>

Building Biomolecules¶

In [88]:
without_K = monomer.not_name_K
without_K
Out[88]:
<Selection: 'not name K' from 1k4c (4527 atoms)>
In [89]:
tetramer = buildBiomolecules(header, without_K)
tetramer
Out[89]:
<AtomGroup: 1k4c Selection 'not name K' biomolecule 1 (18108 atoms)>
In [90]:
showProtein(tetramer)

You appear to be running in JupyterLab (or JavaScript failed to load for some other reason). You need to install the 3dmol extension:
jupyter labextension install jupyterlab_3dmol

Out[90]:
<py3Dmol.view at 0x7f456119cc10>