Serverification of Molecular Modeling Applications: the Rosetta Online Server that Includes Everyone (ROSIE)

The Rosetta molecular modeling software package provides experimentally tested and rapidly evolving tools for the 3D structure prediction and high-resolution design of proteins, nucleic acids, and a growing number of non-natural polymers. Despite its free availability to academic users and improving documentation, use of Rosetta has largely remained confined to developers and their immediate collaborators due to the code's difficulty of use, the requirement for large computational resources, and the unavailability of servers for most of the Rosetta applications. Here, we present a unified web framework for Rosetta applications called ROSIE (Rosetta Online Server that Includes Everyone). ROSIE provides (a) a common user interface for Rosetta protocols, (b) a stable application programming interface for developers to add additional protocols, (c) a flexible back-end to allow leveraging of computer cluster resources shared by RosettaCommons member institutions, and (d) centralized administration by the RosettaCommons to ensure continuous maintenance. This paper describes the ROSIE server infrastructure, a step-by-step 'serverification' protocol for use by Rosetta developers, and the deployment of the first nine ROSIE applications by six separate developer teams: Docking, RNA de novo, ERRASER, Antibody, Sequence Tolerance, Supercharge, Beta peptide design, NCBB design, and VIP redesign. As illustrated by the number and diversity of these applications, ROSIE offers a general and speedy paradigm for serverification of Rosetta applications that incurs negligible cost to developers and lowers barriers to Rosetta use for the broader biological community. ROSIE is available at http://rosie.rosettacommons.org

Bigraphical Refinement

We propose a mechanism for the vertical refinement of bigraphical reactive systems, based upon a mechanism for limiting observations and utilising the underlying categorical structure of bigraphs. We present a motivating example to demonstrate that the proposed notion of refinement is sensible with respect to the theory of bigraphical reactive systems; and we propose a sufficient condition for guaranteeing the existence of a safety-preserving vertical refinement. We postulate the existence of a complimentary notion of horizontal refinement for bigraphical agents, and finally we discuss the connection of this work to the general refinement of Reeves and Streader.Comment: In Proceedings Refine 2011, arXiv:1106.348

Serverification of Molecular Modeling Applications: The Rosetta Online Server That Includes Everyone (ROSIE)

The Rosetta molecular modeling software package provides experimentally tested and rapidly evolving tools for the 3D structure prediction and high-resolution design of proteins, nucleic acids, and a growing number of non-natural polymers. Despite its fre

Serverification of Molecular Modeling Applications: The Rosetta Online Server That Includes Everyone (ROSIE)

The Rosetta molecular modeling software package provides experimentally tested and rapidly evolving tools for the 3D structure prediction and high-resolution design of proteins, nucleic acids, and a growing number of non-natural polymers. Despite its fre

Accurate positioning of functional residues with robotics-inspired computational protein design.

SignificanceComputational protein design promises to advance applications in medicine and biotechnology by creating proteins with many new and useful functions. However, new functions require the design of specific and often irregular atom-level geometries, which remains a major challenge. Here, we develop computational methods that design and predict local protein geometries with greater accuracy than existing methods. Then, as a proof of concept, we leverage these methods to design new protein conformations in the enzyme ketosteroid isomerase that change the protein's preference for a key functional residue. Our computational methods are openly accessible and can be applied to the design of other intricate geometries customized for new user-defined protein functions

Examples of re-usable features and widgets shared across ROSIE servers.

<p>(<b>a</b>) Global job queue page, which can be filtered by specific application (e.g., docking). (<b>b</b>) Self-registration (not required). (<b>c</b>) Coordinate file uploader using Protein Databank format, (<b>d</b>) Automatic visualization of uploaded coordinate file, (<b>e</b>) Score vs. root mean squared deviation plotting widget, (<b>f</b>) Automatic rendering of final models, which can be customized by developer for specific applications (in this case, RNA <i>de novo</i> modeling).</p