> Let me put it this way. Suppose you were reading a paper about someone > else's structures. Which of these two statements would be more useful: > 1) The RMSD for sidechain atoms between apo and holo was 0.678 Å. > or > 2) Only two residues exhibited a significant change of conformation: > the Asn XXX carboxamide flipped 180 degrees allowing ND to act as > H-bond donor to ligand atom FOO; the Lys YYY sidechain occluded > the ligand binding site in the apo structure but extends into the > solvent when the ligand is bound.
Certainly, in a paper, specific and detailed information regarding differences in particular side chain conformations would be more useful and biologically relevant than merely quoting an overall global measure of side chain dissimilarities. I am sure that no-one would think of making standalone statements such as "the average RMSD of side chain atoms is 0.678Å". However, it can be useful to calculate side chain RMSD for various purposes, whether in a publication, or simply for personal use during the course of a comparative structural analysis. It is more meaningful if side chain RMSD is calculated using a local coordinate frame (i.e. after local superposition), resulting in a measure which is independent of global conformation. This is only meaningful in cases where the backbone of the compared structures is locally very similar. For example, if this is performed for sequence-identical structures in different global conformations, then it is possible to use local side chain RMSD to identify and visualise the side chain conformational (dis)similarity between corresponding residues. Such information can be hard for humans to otherwise discern visually, since our interpretation is not independent of the superposition used to visualise the structures. Such information allows us to easily tell whether observed differences are due to differences in the backbone conformation, or differences in side chains, and can be easily visualised by colouring residues according to the side chain dissimilarity score. Certainly, if structures are practically near-identical in net local backbone structure, then interesting information can be achieved by moving to the higher level of structural resolution of side chain atoms. Furthermore, if wanting to compare a class of structures, all of which have highly conserved backbones, information regarding the overall similarity of side chain conformations may help in identifying or quantifying intraclass (dis)similarities. > For residues where the two sequences are > not identical, how do you even calculate an RMSD for sidechain atoms? For sure, comparing side chains becomes less meaningful if the sequences are not identical - this would not be useful in most cases. Nevertheless, if the backbone is practically identical then some researchers performing structural comparisons may want to achieve some way of visualising differences in general side chain orientations. This can be achieved by considering the difference between average positions of side chain atoms between the compared residues, after local backbone superposition. Whilst interpretation would have to be thought about very carefully, such analyses can provide useful information that would be very hard for us to otherwise obtain (e.g. regarding side chain signalling patterns). Considering side chain RMSD requires careful consideration, but can provide useful information. Regards Rob On 13 Jan 2012, at 18:40, Ethan Merritt wrote: > On Friday, January 13, 2012 09:07:07 am Appu kumar wrote: >> Firstly thanks to Robert Nicholls for making me aware of the software >> necessary for side chain RMSD calculation. I have installed and now going >> through manual to use it for exploiting the structural differences. Thanks >> a lot. >> >> Secondly, for Ethan Merritt, I am seeking the information for comparing the >> side chains RMSD for better comparison of structure. Please correct me if i >> am wrong, i want to elaborate more on what i am thinking. If we have refine >> the structure well so that issue of rotamers are fixed > > Sorry, I don't know what you mean when you say "the issue of rotamers are > fixed". > >> , then it is >> possible to take the advantage of side chain orientation for correctly >> understanding the trivial differences between homologous proteins and such >> differences harbouring good piece information for understanding protein >> structure-function relationship. Any kind of suggestion would be highly >> appreciated. > > Let me put it this way. Suppose you were reading a paper about someone > else's structures. Which of these two statements would be more useful: > 1) The RMSD for sidechain atoms between apo and holo was 0.678 Å. > or > 2) Only two residues exhibited a significant change of conformation: > the Asn XXX carboxamide flipped 180 degrees allowing ND to act as > H-bond donor to ligand atom FOO; the Lys YYY sidechain occluded > the ligand binding site in the apo structure but extends into the > solvent when the ligand is bound. > > Your comparison apparently involves a pair of homologs rather than a > pair of holo/apo structures, but I suggest to you that RMSD is even > more useless in this case. For residues where the two sequences are > not identical, how do you even calculate an RMSD for sidechain atoms? > > Ethan > >> >> Thank you >> Appu >> >> On 13 January 2012 21:53, Ethan Merritt <[email protected]> wrote: >> >>> On Friday, 13 January 2012, Appu kumar wrote: >>>> Dear ccp4 users, >>>> Would you please guide me how to calculate >>>> the RMSD of side chains alone without considering C-alpha backbone. >>>> Is/are there any program/programs availble which do this job. I want >>>> to know the RMSD of side chains for protein comparison. >>> >>> What is the question that you are trying to answer? >>> If you are going to disregard the mainchain position, then >>> I would guess that you'd be better off comparing rotamer >>> classes than comparing coordinates. >>> >>> Ethan >>> >>> >>>> >>>> Thank you in advance. >>>> Appu >>>> >>> >>> >> > > -- > Ethan A Merritt > Biomolecular Structure Center, K-428 Health Sciences Bldg > University of Washington, Seattle 98195-7742
