NMR Structure Calculation Using XPLOR-NIH as a Modern Molecular Dynamic's Engine for ARIA2 - ARIAXC

The primary objective of this project was to enhance ARIA2 structure calculation protocol by integrating a more advanced molecular dynamics engine and scripting interface (python), utilising the molecular dynamics program XPLOR. This update aims to improve ARIA2's relevance and applicability to contemporary methods of structural calculation by incorporating the larger variety of structural constraints available in XPLOR such as PREs, SAX data and chemical shift forcefields, .

ARIA2 is an iterative structure calculation program that generates structures based on the most common NMR measurement available, nOes (Nuclear Overhauser Effect), calculating structures and undertaking automatic nOe assignment, using either cartesian or torsion angle, dynamics. However, CNS the molecular dynamics engine that powers ARIA2 is no longer developed and does not have support for the latest molecular dynamics protocols.

A new version ARIA2 ARIA-XC has been developed which uses CNS's parent program XPLOR, which continues to be developed as XPLOR-NIH and contains more modern force fields for working with PREs, Solvent PREs, SAX envelopes and chemical shifts that are not available in CNS. As the scripting interface for XPLOR -NIH is Python2.7 the protocols used by ARIA-XC have been converted to use python as their programming interface. This has further advantages as Python, as opposed to XPLORscipt, is a widely used language when coding programs and is the main scripting language for ARIA.

Side by side comparison between ARIA-XC and ARIA has been carried out as the programs were debugged to ensure that the results from calculations were consistent. This has been carried out using the Werner Tudor domain test set of restraints from ARIA and was supported by the development of the test program RollinStone and a new compassion technique for structure calculation called Structure Injection.

Finally, results from comparisons of the Werner test set show identical structures being calculate with ARIA-XC albeit with the requirement to currently use longer simulated annealing periods.