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2019-05-13T09:31:21Z

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An analysis of the hydrogen-bonding network can provide useful structural information in many situations. For example, it can be used to classify minima (and hence colour disconnectivity graphs) or analyse which contacts are important in protein/ligand binding and identify possible mutations to make. With [[AMBER]], this is done using the ''ptraj'' tool. You can find a full listing of ''ptraj'' functionality in the [[AMBER]] tools manual [http://ambermd.org/doc11/AmberTools.pdf AMBER Tools here].

Running a hydrogen-bond analysis is broken into three stages, preparing the ptraj input, running the analysis and analysing the output. This tutorial will cover the first two stages, as analysing the output is highly system and purpose specific!

== Preparing the ptraj input ==
A ''ptraj'' input file for hydrogen bond analysis is broken into three parts:
# reading in the structure to be analysed
# defining donor and acceptor atoms
# running the hbond analysis

We are going to write a script which will then be passed to 'ptraj' to run the analysis. In this example, we will call it ''hbond.in''.

=== Reading in the structure to be analysed ===
''ptraj'' is able to read in both PDB and AMBER .rst format files. Here we will use PDB files. To read a PDB file into ''ptraj'', we simply use the ''trajin'' command:

<pre>
#-- READING IN A SINGLE FILE
trajin A_Netherlands_602_2009_DG222_0_SIA26GAL14NAG_OME_resp_md1.pdb
</pre>

When doing a hydrogen-bond analysis, you need to decide whether you are interested in the bonding within a single structure (for classifying minima for example), or average properties of many minima (looking at hydrogen-bond occupation). You can read as many PDB files in as you'd like, just by adding additional ''trajin'' lines. For example:

<pre>
#-- READING IN 10 FILES
trajin A_Netherlands_602_2009_DG222_0_SIA26GAL14NAG_OME_resp_md1.pdb
trajin A_Netherlands_602_2009_DG222_0_SIA26GAL14NAG_OME_resp_md2.pdb
trajin A_Netherlands_602_2009_DG222_0_SIA26GAL14NAG_OME_resp_md3.pdb
trajin A_Netherlands_602_2009_DG222_0_SIA26GAL14NAG_OME_resp_md4.pdb
trajin A_Netherlands_602_2009_DG222_0_SIA26GAL14NAG_OME_resp_md5.pdb
trajin A_Netherlands_602_2009_DG222_0_SIA26GAL14NAG_OME_resp_md6.pdb
trajin A_Netherlands_602_2009_DG222_0_SIA26GAL14NAG_OME_resp_md7.pdb
trajin A_Netherlands_602_2009_DG222_0_SIA26GAL14NAG_OME_resp_md8.pdb
trajin A_Netherlands_602_2009_DG222_0_SIA26GAL14NAG_OME_resp_md9.pdb
trajin A_Netherlands_602_2009_DG222_0_SIA26GAL14NAG_OME_resp_md10.pdb
</pre>

=== Defining donor and acceptor atoms ===
You need to tell ''ptraj'' which atoms to consider as donors and acceptors. This is done using the mask syntax that is common in [[AMBER]]. If you're working on a protein, comprised entirely of standard amino acids, with no custom ligand involved, you simply need to define the standard donor-acceptor pairs for the sidechains and backbone:

<pre>
#-- DONORS from standard amino acid sidechains
donor mask :GLN@OE1
donor mask :GLN@NE2
donor mask :ASN@OD1
donor mask :ASN@ND2
donor mask :TYR@OH
donor mask :ASP@OD1
donor mask :ASP@OD2
donor mask :GLU@OE1
donor mask :GLU@OE2
donor mask :SER@OG
donor mask :THR@OG1
donor mask :HIS@ND1
donor mask :HIE@ND1
donor mask :HID@NE2

#-- ACCEPTORS from standard amino acid sidechains
acceptor mask :ASN@ND2 :ASN@HD21
acceptor mask :ASN@ND2 :ASN@HD22
acceptor mask :TYR@OH :TYR@HH
acceptor mask :GLN@NE2 :GLN@HE21
acceptor mask :GLN@NE2 :GLN@HE22
acceptor mask :TRP@NE1 :TRP@HE1
acceptor mask :LYS@NZ :LYS@HZ1
acceptor mask :LYS@NZ :LYS@HZ2
acceptor mask :LYS@NZ :LYS@HZ3
acceptor mask :SER@OG :SER@HG
acceptor mask :THR@OG1 :THR@HG1
acceptor mask :ARG@NH2 :ARG@HH21
acceptor mask :ARG@NH2 :ARG@HH22
acceptor mask :ARG@NH1 :ARG@HH11
acceptor mask :ARG@NH1 :ARG@HH12
acceptor mask :ARG@NE :ARG@HE
acceptor mask :HIS@NE2 :HIS@HE2
acceptor mask :HIE@NE2 :HIE@HE2
acceptor mask :HID@ND1 :HID@HD1
acceptor mask :HIP@ND1,NE2 :HIP@HE2,HD1

#-- Backbone donors and acceptors
# N-H for prolines do not exist so need to exclude :PRO@N from the acceptor mask
donor mask '@O'
acceptor mask '!:PRO & @N' '@H'

#Terminal residues have different atom names - OXT is only present in termini so can use always
donor mask @OXT
#This assumes there is only one protein segment i.e. if there was a terminal BEFORE the ligand
#you would need to add more residue numbers e.g. 'acceptor mask :1,20@N :1,20@H1' etc
acceptor mask :1@N :1@H1
acceptor mask :1@N :1@H2
acceptor mask :1@N :1@H3
</pre>

<pre>
DONOR ACCEPTORH ACCEPTOR
atom# :res@atom atom# :res@atom atom# :res@atom %occupied distance angle
| 3969 :255@O1A | 1481 :98@HG1 1480 :98@OG1 | 100.00 2.629 ( 0.10) 16.33 ( 4.50)
</pre>

From the [http://ambermd.org/doc11/AmberTools.pdf AMBER Tools manual] (AMBER 11 version)
<pre>
hbond [<dataset name>] [out <filename>] <mask> [angle <cut>] [dist <cut>] [avgout <avgfilename>]

Search for hydrogen bond donor and acceptor atoms in the region speciﬁed by <mask>
(currently following the simplistic criterion that “hydrogen bonds are FON”, i.e., hydrogens
bonded to F, O, and N atoms are considered) and calculate the number of hydrogen bonds
formed for each frame, writing the results to the ﬁle speciﬁed by “out”. Hydrogen bonds are
considered to have the form:

Acceptor ... Hydrogen-Donor

and are determined via the distance between the heavy atoms using a cutoff of 3.0 Å (or the
value speciﬁed by “dist”) and the angle between the acceptor, hydrogen, and donor atoms using
a cutoff of 135° (or the value speciﬁed by “angle”)
</pre>

Performing a hydrogen-bond analysis - Revision history

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