Protein Design

A short video introduction to proteins made by the University of Washington.

Introduction to Protein Design and Protein Design Algorithms

Dr. Baker’s iBiology video talk was recorded in April 2014.

From iBiology: David begins his talk by describing two reciprocal research problems. The first is how to predict the 3 dimensional structure of a protein from a specific amino acid sequence, while the second is how to determine the amino acid sequence that will generate a new protein designed to have a specific structure. The Baker lab is addressing the second of these challenges by developing computer programs (such as Rosetta@Home) that calculate the lowest energy, or most likely, structures for differently folded amino acid sequences. Baker explains how his lab can design a new protein structure, not found in nature, and using the computer programs they have developed, determine the amino acid structure. It is then possible to back translate to the DNA sequence and synthesize the gene that can then by used to make the protein. When the structures of these synthesized proteins are determined by crystallography and compared to the predicted structures of the designed proteins, they are found to overlap very closely demonstrating that the protein design algorithms work well.

In the second of his talks, David tells us how his lab has moved beyond designing new protein structures to designing new protein functions. The first example he describes is the development of an inhibitor of the influenza virus. The Baker lab designed a protein structure that fits into a highly conserved region of the hemagglutinin protein found on the surface of influenza. Preliminary lab data suggests that this designed protein protects mice from infection with the flu virus. David also describes experiments in which proteins were designed to fit together and build multicomponent materials such as nanocages, nanolayers and nanowires.

Using Design Tracker

Design Tracker is used to manage protein production orders in our Structured Science Protein Core (SSPC) and other associated partnering facilities such as the UW Protein Production Group (UW PPG, located in SLU). Design Tracker captures all aspects of designed protein production from the atomic coordinate set of the model of the designed protein to the synthetic gene order encoding the protein to all aspects of expression vector cloning, protein production, purification, and biophysical characterization.

Watch a short tutorial, led by SSPC leader Lauren Carter on how to use the Design Tracker software.

Rosetta 101: Basic Concepts in Rosetta Core Functionality

Can also be called: Everything you always wanted to know about Rosetta, but were afraid to ask!

Watch an hour long primer on the core concepts of the Rosetta software algorithms, explained in plain language without the complex computational terms. Featuring IPD postdoctoral fellows Dr. Vikram Mulligan and Dr. Indigo Chris King.

Rosetta 201: Introduction to Rosetta Development – presented by Dr. Vikram Mulligan

Rosetta 201provides an overview of concepts that new Rosetta developers (particularly those without a computer science background) will need to understand in order to start creating new Rosetta algorithms. The lecture covers some important C++ concepts as they apply to Rosetta, Rosetta-specific code conventions and idiosyncrasies, the organization of the Rosetta libraries and location in the code of the most commonly-used Rosetta classes, and the use of unit and integration tests to prevent new (or old) code from breaking. The lecture also explains the workflow for managing branches and for merging new code into the master branch using Git, pull requests, and the testing server. Finally, the lecture explains how code should be documented, both with in-code Doxygen tags and on the Rosetta user-focused help Wiki.

Compute Support at the Institute for Protein Design

Compute Support at the Institute for Protein Design – presented by Dr. Darwin Alonso, Computing Core Systems Administrator

The UW Institute for Protein Design requires colossal amounts of compute power and data storage in its quest to predict existing protein structure and design new proteins and binders. The lion’s share of our compute capacity relies on our presence in the UW Towers Data Center. The data center and associated cooling and power capacity:

– provides the IPD with infrastructure to house the group’s own in-house clusters and data storage systems
– high bandwidth access to UW IT’s high performance computer cluster (Hyak) and archival storage
– high bandwidth access to an number of “cloud” based compute
resources, including BOINC
– an interface for the IPD’s web presences and a number of services
provided to the greater scientific community

Library Structure 2 – Presented by Hahnbeom Park

C++ Classes #2 – Presented by Vikram Mulligan


Graphs – Presented by Alex Ford

Library Structure 4: Simple Protocols – Presented by Tom Linsky

Library Structure 6 – Presented by Frank DiMaio

Adding Code to Rosetta – Presented by Vikram Mulligan

Library Structure 5 – Presented by Daniel Silva Adriano

Library Structure 7: Miscellaneous Protocols – Presented by Indigo Chris King

Intro to Protein Structure Prediction and Design including Review of Protein Structure

Protein Geometry; Molecular Energies and Forces (p1)

Molecular Energies and Forces (part 2)

Molecular Energies and Forces (part 3)

Ab-Initio Protein Structure Prediction (part 1)

Ab-Initio Protein Structure Prediction (part 2)

Refinement of Protein Structures

Rotamer Libraries and Side-chain Packing

Protein-Protein Docking

Loop Modeling

Non-Protein Molecules in Rosetta

Modeling Membrane Proteins in Rosetta