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The RosettaCon 2014 Collection: Developing tools in Macromolecular Modeling Software

The Rosetta developer community meets annually to discuss the advances in the Rosetta modeling software, a suite that models and helps design macromolecules. Today we announce the launch of the next exciting collection, RosettaCon 2014, comprising 11 articles detailing recent scientific advancements made by developers that use Rosetta.


Image Credit: 10.1371/journal.pone.0023947
Image Credit: 10.1371/journal.pone.0023947

The Rosetta macromolecular modeling software is a versatile, rapidly developing set of tools that are now being routinely utilized to address state-of-the-art research challenges in academia and industrial research setting.


PLOS and the RosettaCommons labs have partnered together since 2010 to produce three collections describing the results of the Rosetta conferences. PLOS ONE launched the first of these collections, RosettaCon 2010, which made the latest research on protocols used to create macromolecular models available to all. This was followed by the RosettaCon 2012 Collection which highlighted further developments within the community.


This year’s collection features 11 research articles recently published in PLOS ONE and PLOS Computational Biology focusing upon four broad categories: protein structure prediction, membrane proteins, scientific benchmarks, and docking. What they all show is the depth and diversity of modeling applications present in the Rosetta Macromolecular Code framework.


Protein Structure Prediction

The structural prediction of monomeric, soluble proteins is still an unsolved problem, notwithstanding notable recent advances. One important necessity in computational prediction protocols is reducing the high dimensional search space during simulations. Examples of recent successful approaches which use the incorporation of structural restraints derived from phylogeny or low-resolution experiments are included in the collection from Braun et al. and Huber and colleagues.


Membrane proteins

The design and modeling of membrane proteins is an emerging research area. Gray and colleagues describe a new framework, RosettaMP, for computational modeling and design of membrane protein structures, integrated into the Rosetta3 software suite. This framework includes a set of tools for representing the membrane bilayer, moving the protein, altering its sequence, and estimating free energies.


Scientific benchmarks

Development of accessible, standard benchmarks for different end uses has the potential to increase the speed of method development, and aid reproducibility. To help tackle this large issue, the Kortemme lab has developed a centralized web resource for standardized benchmark datasets (https://kortemmelab.ucsf.edu/benchmarks). This resource includes three main sets of benchmarks; tests estimating the energetic effects upon mutation, tests for structure prediction, and ones for protein design. To further demonstrate the utility of using benchmark sets, Ollikainen et al. developed a benchmark in order to test different protein design protocols on the re-design of enzyme substrate specificity.



A significant issue limiting the success of both protein-protein and protein-small molecule docking is the large size and ruggedness of the search space. A number of articles within the collection focus on the sampling and scoring issues in docking. For example, Zhang et al. show the application of replica exchange and other advance sampling techniques to increase the efficiency of Monte Carlo search during docking and Bazzoli et al. show that the use of two recent enhancements to the Rosetta energy function can markedly improve the ability to identify small-molecule inhibitors of protein-protein interactions.


This new RosettaCon collection continues to help serve the community in an effort to ensure that newly developed protocols are as usable as more established workflows, are transparent, and are accurately documented even in an active development environment.


This post has been adapted from “Introduction to the Rosetta Special Collection” which serves as a more in-depth overview of the new collection.





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