Increased usability, algorithmic improvements and incorporation of data mining for structure calculation of proteins with REDCRAFT software package

Abstract

Background Traditional approaches to elucidation of protein structures by Nuclear Magnetic Resonance spectroscopy (NMR) rely on distance restraints also known as Nuclear Overhauser effects (NOEs). The use of NOEs as the primary source of structure determination by NMR spectroscopy is time consuming and expensive. Residual Dipolar Couplings (RDCs) have become an alternate approach for structure calculation by NMR spectroscopy. In previous works, the software package REDCRAFT has been presented as a means of harnessing the information containing in RDCs for structure calculation of proteins. However, to meet its full potential, several improvements to REDCRAFT must be made. Results In this work, we present improvements to REDCRAFT that include increased usability, better interoperability, and a more robust core algorithm. We have demonstrated the impact of the improved core algorithm in the successful folding of the protein 1A1Z with as high as ±4 Hz of added error. The REDCRAFT computed structure from the highly corrupted data exhibited less than 1.0 Å with respect to the X-ray structure. We have also demonstrated the interoperability of REDCRAFT in a few instances including with PDBMine to reduce the amount of required data in successful folding of proteins to unprecedented levels. Here we have demonstrated the successful folding of the protein 1D3Z (to within 2.4 Å of the X-ray structure) using only N-H RDCs from one alignment medium. Conclusions The additional GUI features of REDCRAFT combined with the NEF compliance have significantly increased the flexibility and usability of this software package. The improvements of the core algorithm have substantially improved the robustness of REDCRAFT in utilizing less experimental data both in quality and quantity.

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“…Mining of the PDBMine can quickly produce the conventional Ramachandran plots [18], and more extensive correlative knowledge, such as the relationship between dihedrals between all sets of adjacent residues. PDBMine has also facilitated the discovery of absent k-mer sequences [19,20] in the PDB.…”

Current trend and development in bioinformatics research

“…Traditional approaches to elucidation of protein structures by NMR spectroscopy are time consuming and expensive, however, the faster and more cost-effective methods are critical in the development of personalized medicine. Cole et al improved the REDRAFT software package in the important areas of usability, accessibility, and the core methodology which resulted in the ability to fold proteins [3].…”