Publications

De novo design of potent and selective mimics of IL-2 and IL-15.

Published in Nature, 2019

We describe a de novo computational approach for designing proteins that recapitulate the binding sites of natural cytokines, but are otherwise unrelated in topology or amino acid sequence. We use this strategy to design mimics of the central immune cytokine, IL-2. Read more

Recommended citation: Silva DA*, Yu S*, Ulge U*, Spangler JB*, Jude KM, Labão–Almeida C, Ali L, Quijano–Rudio A, Ruterbusch M, Leung I, Biary T, Marcos E, Walkey CD, Weitzner BD, Carter L, Stewart L, Riddell S, Pepper M, Bernardes GJL, Dougan M, Garcia KC, Baker D (2018) “De novo design of potent and selective mimics of IL-2/IL-15,” Nature. 565(7738), 186–191 DOI: 10.1038/s41586-018-0830-7 (* equal contribution authors)

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

Published in PLOS Computational Biology, 2018

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. Read more

Recommended citation: Adolf-Bryfogle J, Kalyuzhniy O, Kubitz M, Weitzner BD, Hu X, Adachi Y, Schief WR, Dun- brack RL, Jr (2018) “Rosetta Antibody Design (RAbD): A General Framework for Computational Antibody Design,” PLoS Comput. Biol. 14(4): e1006112. DOI: 10.1371/journal.pcbi.1006112

Modeling and docking antibody structures with Rosetta

Published in Nature Protocols, 2017

We describe Rosetta-based computational protocols for predicting the 3D structure of an antibody from sequence (RosettaAntibody) and then docking the antibody to protein antigens (SnugDock). Read more

Recommended citation: Weitzner BD*, Jeliazkov JR*, Lyskov S*, Marze N, Kuroda D, Frick R, Adolf-Bryfogle J, Biswas N, Dunbrack RL, Jr, Gray JJ (2017) “Modeling and docking antibody structures with Rosetta,” Nat. Protoc. 12(2), 401–16. DOI: 10.1038/nprot.2016.180 (* equal contribution authors)

Accurate structure prediction of CDR H3 loops enabled by a novel structure-based C-terminal constraint

Published in The Journal of Immunology, 2016

We use structural parameters gleaned from previous work to develop a new biasing constraint that, when applied to a benchmark set of high-quality CDR H3 loops, enables the production of high-quality structural models de novo. Read more

Recommended citation: Weitzner BD, Gray JJ (2017) “Accurate structure prediction of CDR H3 loops enabled by a novel structure-based C-terminal constraint,” J. Immunol. 198(1), 505–15. DOI: 10.4049/jimmunol.1601137

A framework to simplify combined sampling modes in Rosetta

Published in PLOS ONE, 2015

To streamline the incorporation of diverse structural constraints, we developed the Broker: an extension of the Rosetta macromolecular modeling suite that can express a wide range of protocols using constraints by combining small, independent modules, each of which implements a different set of constraints. Read more

Recommended citation: Porter JR, Weitzner BD, Lange OF (2015) “A framework to simplify combined sampling modes in Rosetta,” PLOS ONE 10(9): e0138220. DOI: 10.1371/journal.pone.0138220

An integrated framework advancing membrane protein modeling and design

Published in PLOS Computational Biology, 2015

We present RosettaMP to provide a general membrane representation that interfaces with scoring, conformational sampling, and mutation routines that can be easily combined to create new protocols. Read more

Recommended citation: Alford RF*, Koehler Leman J*, Weitzner BD, Duran AM, Tilley DC, Elazar A, Gray JJ (2015) “An integrated framework advancing membrane protein modeling and design,” PLOS Comput. Biol. 11(9): e1004398. DOI: 10.1371/journal.pcbi.1004398 (* equal contribution authors)

The origin of CDR H3 structural diversity

Published in Structure, 2015

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. Read more

Recommended citation: Weitzner BD, Dunbrack RL, Jr, Gray JJ (2015) “The origin of CDR H3 structural diversity,” Structure 23(2), 302–11. DOI: 10.1016/j.str.2014.11.010

Blind prediction performance of RosettaAntibody 3.0: Grafting, relaxation, kinematic loop modeling, and full CDR optimization

Published in PROTEINS: Structure, Function, and Bioinformatics, 2014

We report the performance of RosettaAntibody in the AMA‐II. In nearly every case, RosettaAntibody produced accurate, physically realistic models. The causes of model errors are explored in order to make further improvements to RosettaAntibody. Read more

Recommended citation: Weitzner BD*, Kuroda D*, Marze N, Xu J, Gray JJ (2014) “Blind prediction performance of RosettaAntibody 3.0: Grafting, relaxation, kinematic loop modeling, and full CDR optimization,” Proteins 82(8), 1611–23. DOI: 10.1002/prot.24534 (* equal contribution authors)

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

Published in PLOS ONE, 2013

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. Read more

Recommended citation: Lyskov S, Chou FC, Conchúir SÓ, Der BS, Drew K, Kuroda D, Xu J, Weitzner BD, Renfrew PD, Sripadeevong P, Borgo B, Havranek JJ, Kuhlman B, Kortemme T, Bonneau R, Gray JJ, Das R (2013) "Serverification of Molecular Modeling Applications: The Rosetta Online Server That Includes Everyone (ROSIE)," PLOS ONE 8(5): e63906. DOI: 10.1371/journal.pone.0063906

Real-time PyMOL visualization for Rosetta and PyRosetta

Published in PLOS ONE, 2011

We developed a novel solution based on transmitting biomolecular structure and energy information via UDP sockets to enable real-time visualization of Rosetta simulations in PyMOL. Read more

Recommended citation: Baugh EH, Lyskov S, Weitzner BD, Gray JJ (2011) “Real-time PyMOL visualization for Rosetta and PyRosetta,” PLOS ONE 6(8): e21931. DOI: 10.1371/journal.pone.0021931

Benchmarking and analysis of protein docking performance in Rosetta v3.2

Published in PLOS ONE, 2011

We present the most extensive benchmarking of the RosettaDock module to date and test capabilities of RosettaDock 3.2 against Docking Benchmark 3.0. Read more

Recommended citation: Chaudhury S, Berrondo M, Weitzner BD, Muthu P, Bergman H, Gray JJ (2011) “Benchmark- ing and analysis of protein docking performance in Rosetta v3.2,” PLOS ONE 6(8): e22477. DOI:10.1371/journal.pone.0022477

An unusually small dimer interface is observed in all available crystal structures of cytosolic sulfotransferases

Published in PROTEINS: Structure, Function, and Bioinformatics, 2009

Analysis of the crystal packing interfaces in all 28 available crystal structures consisting of 17 crystal forms shows that the unusually small dimer interface previously identified by Petrotchenko et al. occurs in all of them. Read more

Recommended citation: Weitzner B, Meehan T, Xu Q, Dunbrack R (2009) “An unusually small dimer interface is observed in all available crystal structures of cytosolic sulfotransferases,” Proteins. 75(2), 1097–134. DOI:0.1002/prot.22347