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I'm a electrical engineer and I'm learning about bioinformatics. I was reading this paper that uses the last heavy atom to search for active sites of a protein but what would be a heavy atom? Is it all atoms but hydrogen? Atoms heavier than carbon? And how do I know which is the last heavy atom?

The article: http://bioinformatics.oxfordjournals.org/content/early/2014/11/08/bioinformatics.btu746.full.pdf+html

It talks about the last heavy atom under Materials and Methods 2.1.1 Individual Representation and Population Initialization

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    $\begingroup$ Your description is not quite clear. Can you please give the complete reference for the article you're reading, and also the precise quote? $\endgroup$ – Roland Sep 8 '15 at 17:28
  • $\begingroup$ bioinformatics.oxfordjournals.org/content/early/2014/11/08/… $\endgroup$ – João Areias Sep 8 '15 at 17:52
  • $\begingroup$ It's under materials and methods on 2.1.1 Individual representation and population initialization $\endgroup$ – João Areias Sep 8 '15 at 17:53
  • $\begingroup$ I haven't heard of this concept before, but it looks like the LHA is a reference atom at the "end" of the amino acid side chain. The precise definition appears to be empirical / heuristic, see cbi.cnptia.embrapa.br/SMS/STINGm/help/lha.html $\endgroup$ – Roland Sep 8 '15 at 18:15
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As mentioned in the comments by Roland, this term is not common and is first used by the authors of the mentioned paper (also the package mentioned by Roland in comments - STING).

From this link you can find the definition of the Last Heavy Atom which is possibly the most distal non-hydrogen (N, C, O, S) atom in the amino-acid side chain.

$$\begin{array}{|c|c|c|c|} \hline Ala\ :\ C_\beta & Asp\ :\ O_{\delta^2} &Trp\ :\ C_{\eta^2} &Asn\ :\ N_{\delta^2} \\ \hline Lys\ :\ N_\zeta & Glu\ :\ O_{\epsilon^2} & Ser\ :\ O_\gamma & Gln\ :\ N_{\epsilon^2} \\ \hline Cys\ :\ S_\gamma & His\ :\ N_{\epsilon^2} & Tyr\ :\ O_\eta & Val\ :\ C_{\gamma^2} \\ \hline Gly\ :\ C_\alpha & Leu\ :\ C_{\delta^2} & Met\ :\ C_\epsilon & Ile\ :\ C_{\delta^1} \\ \hline Arg\ :\ N_{\eta^2} & Phe\ :\ C_\zeta & Pro\ :\ C_\delta & Thr\ :\ C_{\gamma^2} \\ \hline \end{array}$$

They have mentioned in the same link that:

If in any of the PDB files (to be analyzed by the BLUE STAR STING components) that specific atom (LHA) is missing in the record, then our algorithms will search for the next closer atom in the side chain that would be considered as the LHA.


The exact location of some of the abovementioned atoms.

Some of the locations might be confusing. So I am just indicating what these are, for a few the amino acids (especially for the branched and cyclic side chains).
[Images reproduced from here.]

Arginine

enter image description here

The terminal nitrogens $\eta^1$ and $\eta^2$ are symmetric and the atom that is actually (stereochemically) the most distal is considered the LHA, as inferred from the protein structure. The second choice, obviously is the $\eta^1$-Nitrogen.

Aspartic acid

enter image description here

The two terminal oxygens ($\delta^1$ and $\delta^2$) in the ionized form are equivalent (also otherwise because of resonance). The actual distal atom would be labelled as $\delta^2$

you can extrapolate the same for Glutamic acid

Histidine

enter image description here

$\epsilon^2$ refers to the pyrollic nitogen. .

Leucine

enter image description here

The last carbons ($\delta^1$ and $\delta^2$) are equivalent and the choice is based on the actual distance. Extrapolate for valine

Phenylalanine

enter image description here

$\zeta$ refers to the carbon in the para-position of the benzene ring. For tyrosine the LHA is the oxygen of the para-OH in the benzene ring.

Tryptophan

enter image description here

Proline

enter image description here

For Aspargine and Glutamine the LHA is the amide nitrogen of the side chain.

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    $\begingroup$ From a search of Web of Science, it appears that LHA is a term that has been coined by informaticians and is not something that is used in Biochemistry or Organic Chemistry. There are only three articles that are under the topic "Last Heavy Atom," and all three are Informatics Journals. The abstract of this article gives a decent "definition" of the term. link.springer.com/article/10.1186/1758-2946-1-13 $\endgroup$ – AMR Sep 10 '15 at 2:39
  • $\begingroup$ @AMR Yes it is not a standard term. There are quite some articles that use this term but I guess they are the ones using the abovementioned protein structural biochemistry package. $\endgroup$ – WYSIWYG Sep 10 '15 at 5:23
  • $\begingroup$ Seems a bit weird for the cyclic sidechains (except proline), given that they can rotate around the Calpha-Cbeta bond... $\endgroup$ – gilleain Mar 14 '17 at 16:43

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