Publications

Macromolecular modeling and design in Rosetta: recent methods and frameworks.

Koehler Leman J, Weitzner BD, Lewis SM, et al.
Nature Methods, 2020 : https://doi.org/10.1038/s41592-020-0848-2

We discuss the methods developed in the last five years, involving the latest protocols for structure prediction, protein–protein and protein–small molecule docking, protein structure and interface design, loop modeling, the incorporation of various types of experimental data, and modeling of peptides, antibodies and other proteins in the immune system, nucleic acids, non-standard amino acids, carbohydrates, and membrane proteins. We also briefly discuss improvements to the energy function, user interfaces, and usability of the ­­software.

A computational method for design of connected catalytic networks in proteins.

Weitzner BD, Kipnis Y, Daniel AG, et al.
Protein Science, 2019 : https://doi.org/10.1002/pro.3757

Our new method starts from a ChemDraw‐like two‐dimensional representation of the transition state with hydrogen‐bond donors, acceptors, and covalent interaction sites indicated, and all placements of side‐chain functional groups that make the indicated interactions with the transition state, and are fully connected in a single hydrogen‐bond network are systematically enumerated. Used in conjunction with RosettaMatch, this method generates many fully‐connected active site solutions for a set of model reactions that are promising starting points for the design of fully‐preorganized enzyme catalysts.

[PREPRINT] Designing Peptides on a Quantum Computer.

Mulligan VK, et al.
bioRxiv, 2019 : https://doi.org/10.1101/752485

We describe our mapping of the protein design problem to the D-Wave quantum annealer. We present a system whereby Rosetta, a state-of-the-art protein design software suite, interfaces with the D-Wave quantum processing unit to find amino acid side chain identities and conformations to stabilize a fixed protein backbone.

Rosetta Antibody Design (RAbD): A General Framework for Computational Antibody Design

Adolf-Bryfogle J, et al.
PLOS Computational Biology, 2018 : https://doi.org/10.1371/journal.pcbi.1006112

We present RAbD, which can be used to redesign a single CDR or multiple CDRs with loops of different length, conformation, and sequence. We rigorously benchmarked RAbD on a set of 60 diverse antibody–antigen complexes, using two design strategies—optimizing total Rosetta energy and optimizing interface energy alone. We tested RAbD experimentally demonstrating markedly improved binding affinities.

The origin of CDR H3 structural diversity

Weitzner BD, Dubrack RL Jr, Gray JJ
Structure, 2015 : https://doi.org/10.1016/j.str.2014.11.010

To determine why the majority of H3 loops are kinked, we searched a set of non-antibody structures for regions geometrically similar to the residues immediately surrounding the loop. We find that the kink is conserved in the immunoglobulin heavy chain fold because it disrupts β-strand pairing at the base of the loop. Thus, the kink is a critical driver of the observed structural diversity in CDR H3.

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

Lyskov S, Chou FC, et al.
PLOS ONE, 2013 : https://doi.org/10.1371/journal.pone.0063906

Here, we present a unified web framework for Rosetta applications called ROSIE that provides (a) a common user interface for Rosetta protocols, (b) a stable API 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.