Class 10: Structural Bioinformatics (pt. 1)

Author

Aadhya Tripathi (PID: A17878439)

The PDB Database

The Protein Data Bank (PDB) is the main repository of biomolecular structure data. We will see what is in it.

stats <- read.csv("pdb_stats.csv", row.names = 1)
stats

                         X.ray    EM   NMR Integrative Multiple.methods Neutron
Protein (only)          178795 21825 12773         343              226      84
Protein/Oligosaccharide  10363  3564    34           8               11       1
Protein/NA                9106  6335   287          24                7       0
Nucleic acid (only)       3132   221  1566           3               15       3
Other                      175    25    33           4                0       0
Oligosaccharide (only)      11     0     6           0                1       0
                        Other  Total
Protein (only)             32 214078
Protein/Oligosaccharide     0  13981
Protein/NA                  0  15759
Nucleic acid (only)         1   4941
Other                       0    237
Oligosaccharide (only)      4     22

Q1: What percentage of structures in the PDB are solved by X-Ray and Electron Microscopy.

n.sums <- colSums(stats)
n <- n.sums/n.sums["Total"]
round(n, digits=2)

           X.ray               EM              NMR      Integrative 
            0.81             0.13             0.06             0.00 
Multiple.methods          Neutron            Other            Total 
            0.00             0.00             0.00             1.00

round(n["X.ray"] + n["EM"], digits=2)

X.ray 
 0.94

What is the total number of entries in the PDB?

total <- n.sums["Total"]
total

 Total 
249018

Q2: What proportion of structures in the PDB are protein?

n.proteins <- stats$Total[1]
round(n.proteins/total, digits=2)

Total 
 0.86

Using Molstar

We will use the main Molstar viewer online

First view of HIV-Pr dimer with bound inhibitor

Q. Generate and insert an image of the HIV-Pr cartoon representation colored by secondary strucutre, showing the inhibitor (ligand) in ball and stick.

Q. Generate and insert an image showing catalytic ASP 25 residue as ball and stick, and the all-important active site water molecule as space-fill.

HIV-Pr with ASP 25 and active site H2O 308 highlighted.

The Bio3D Package for structural bioinformatics

library(bio3d)

hiv <- read.pdb("1hsg")

  Note: Accessing on-line PDB file

hiv


 Call:  read.pdb(file = "1hsg")

   Total Models#: 1
     Total Atoms#: 1686,  XYZs#: 5058  Chains#: 2  (values: A B)

     Protein Atoms#: 1514  (residues/Calpha atoms#: 198)
     Nucleic acid Atoms#: 0  (residues/phosphate atoms#: 0)

     Non-protein/nucleic Atoms#: 172  (residues: 128)
     Non-protein/nucleic resid values: [ HOH (127), MK1 (1) ]

   Protein sequence:
      PQITLWQRPLVTIKIGGQLKEALLDTGADDTVLEEMSLPGRWKPKMIGGIGGFIKVRQYD
      QILIEICGHKAIGTVLVGPTPVNIIGRNLLTQIGCTLNFPQITLWQRPLVTIKIGGQLKE
      ALLDTGADDTVLEEMSLPGRWKPKMIGGIGGFIKVRQYDQILIEICGHKAIGTVLVGPTP
      VNIIGRNLLTQIGCTLNF

+ attr: atom, xyz, seqres, helix, sheet,
        calpha, remark, call

head(hiv$atom)

  type eleno elety  alt resid chain resno insert      x      y     z o     b
1 ATOM     1     N <NA>   PRO     A     1   <NA> 29.361 39.686 5.862 1 38.10
2 ATOM     2    CA <NA>   PRO     A     1   <NA> 30.307 38.663 5.319 1 40.62
3 ATOM     3     C <NA>   PRO     A     1   <NA> 29.760 38.071 4.022 1 42.64
4 ATOM     4     O <NA>   PRO     A     1   <NA> 28.600 38.302 3.676 1 43.40
5 ATOM     5    CB <NA>   PRO     A     1   <NA> 30.508 37.541 6.342 1 37.87
6 ATOM     6    CG <NA>   PRO     A     1   <NA> 29.296 37.591 7.162 1 38.40
  segid elesy charge
1  <NA>     N   <NA>
2  <NA>     C   <NA>
3  <NA>     C   <NA>
4  <NA>     O   <NA>
5  <NA>     C   <NA>
6  <NA>     C   <NA>

pdbseq(hiv)

  1   2   3   4   5   6   7   8   9  10  11  12  13  14  15  16  17  18  19  20 
"P" "Q" "I" "T" "L" "W" "Q" "R" "P" "L" "V" "T" "I" "K" "I" "G" "G" "Q" "L" "K" 
 21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40 
"E" "A" "L" "L" "D" "T" "G" "A" "D" "D" "T" "V" "L" "E" "E" "M" "S" "L" "P" "G" 
 41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  60 
"R" "W" "K" "P" "K" "M" "I" "G" "G" "I" "G" "G" "F" "I" "K" "V" "R" "Q" "Y" "D" 
 61  62  63  64  65  66  67  68  69  70  71  72  73  74  75  76  77  78  79  80 
"Q" "I" "L" "I" "E" "I" "C" "G" "H" "K" "A" "I" "G" "T" "V" "L" "V" "G" "P" "T" 
 81  82  83  84  85  86  87  88  89  90  91  92  93  94  95  96  97  98  99   1 
"P" "V" "N" "I" "I" "G" "R" "N" "L" "L" "T" "Q" "I" "G" "C" "T" "L" "N" "F" "P" 
  2   3   4   5   6   7   8   9  10  11  12  13  14  15  16  17  18  19  20  21 
"Q" "I" "T" "L" "W" "Q" "R" "P" "L" "V" "T" "I" "K" "I" "G" "G" "Q" "L" "K" "E" 
 22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41 
"A" "L" "L" "D" "T" "G" "A" "D" "D" "T" "V" "L" "E" "E" "M" "S" "L" "P" "G" "R" 
 42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  60  61 
"W" "K" "P" "K" "M" "I" "G" "G" "I" "G" "G" "F" "I" "K" "V" "R" "Q" "Y" "D" "Q" 
 62  63  64  65  66  67  68  69  70  71  72  73  74  75  76  77  78  79  80  81 
"I" "L" "I" "E" "I" "C" "G" "H" "K" "A" "I" "G" "T" "V" "L" "V" "G" "P" "T" "P" 
 82  83  84  85  86  87  88  89  90  91  92  93  94  95  96  97  98  99 
"V" "N" "I" "I" "G" "R" "N" "L" "L" "T" "Q" "I" "G" "C" "T" "L" "N" "F"

Let’s try out the new bio3dview package that is not yet on CRAN. We can use the remotes package to install any R package from GitHub.

Quick Viewing of PDBs

library(bio3dview)
library(NGLVieweR)

sele <- atom.select(hiv, resno=25)

view.pdb(hiv, backgroundColor = "lightgreen",
         highlight = sele, 
         highlight.style = "spacefill") |>
  setSpin()