Hello Suze Ma-- > > 1. I intend to calculate the solution 3D structures of two peptide > macrocycles based on their 1H-1H NOESY data. The first one contains > an ether crosslink (from an exogenous oxygen atom) inserted between > the Trp1-C7 and the Phe3-Cβ while the second one contains a > carbon-carbon crosslink derived from Trp1-C7 and Lys3-Cβ. (for both > structures, see ref: https://doi.org/10.1021/jacs.3c04355). I am > wondering if there are patches to add these two types of > modifications to the structures. I guess addAtom.py is not suitable > for these cases. In addition, I am not sure how to generate the > parameters (e.g. bond, angle, etc) associated with these > intramolecular crosslinks (I understand that the original protein > topology file, e.g. protein-1.0.top, does not contain such > information).
You will need patches along the lines of those used in eginput/PSF_generation/gen*CircPep.py in the Xplor-NIH distribution. I can help with the required patches. But particularly for the ether case, parameters are required - we might borrow those of anisole, if you can find the atomic coordinates of that molecule. For the carbon-carbon crosslink, we can make a decent educated guess. > > 2. To generate distance restraints, I use sparky to assign the NOESY > spectrum and obtain the intensity of NOE signals, which, upon > calibrated by a known interprotein distance (e.g. Thr-HA to Thr-HN, > 2.51 angstrom) and its NOE intensity in my spectrum, only results in > a single list of distances, referred to as d. However, I'm not sure > how to generate the dminus and dplus to define the distance > restraint bounds (d-dminus, d-dplus). I know there are other > methods, such as MARDIGRAS, to generate the bounds. However, I don't > find an available access to these algorithms. Thus, I am asking if > there are other methods to overcome or circumvent the problem in > generating distance restraints bounds for calculations? Usually, the intensity-derived distances are rather qualitative, so that distance bounds would be at least +/- 1 Angstrom, so unless you know otherwise, you might use this value. > > 3. I am wondering is it possible to only rely on the NOE restraints > (and not dihedral restraints or others) to model the structures of > the small peptide macrocycles in my case? If it is theoretically > feasible, how to calculate only with distance restraints and not > other restraints by using fold.py, anneal.py, etc? Simply by > deleting the contents regarding other restraints while only > maintaining the contents regarding distance restraints? Of course, more data is better, but distance-only information can be used by commenting-out or removing sections of the scripts which involve other restraints. best regards-- Charles ######################################################################## To unsubscribe from the XPLOR-NIH list, click the following link: http://list.nih.gov/cgi-bin/wa.exe?SUBED1=XPLOR-NIH&A=1
