David Baker

Overview

David Baker is a protein scientist based at the University of Washington in Seattle, known for computational protein design — using computers to invent proteins that do not exist in nature. He was born in 1962 in Seattle, Washington^[1]. In 2024 the Royal Swedish Academy of Sciences awarded him one half of the Nobel Prize in Chemistry for computational protein design^[1]. At the time of the prize he was affiliated with the University of Washington in Seattle and with the Howard Hughes Medical Institute^[1].

What protein design is

Proteins are chains of amino acids that fold into three-dimensional shapes, and their functions — catalysing reactions, recognising other molecules, carrying signals — follow from those shapes. Natural proteins evolved to keep organisms alive, not to serve human purposes, so anyone who needs a protein with a particular job usually has to search through nature or modify something that already exists. Protein design inverts the problem: start from a desired shape or function and ask which amino acid sequence would fold into it. Because the number of possible sequences is enormous, the search is done on computers, and the output is a candidate that still has to be made and tested in the laboratory.

The 2003 design

The Royal Swedish Academy of Sciences credits Baker with designing a new protein unlike any other in 2003, using computer-based methods he had developed^[1]. The significance lies in the direction of the work: the protein was specified computationally rather than discovered in an organism, which showed that design software could produce a molecule with no natural counterpart. That demonstration underlies the 2024 award, one half of which was given for computational protein design^[1].

Positions and institutions

Baker is the Henrietta and Aubrey Davis Endowed Professor in Biochemistry at the University of Washington^[2], and he also holds adjunct professorships there in genome sciences, bioengineering, chemical engineering, computer science and physics^[2]. He is a Howard Hughes Medical Institute Investigator^[2].

He founded and directs the Institute for Protein Design, which was established at the University of Washington in 2012^[2].

How the lab works

Baker's lab develops protein design software and iterates between computation and laboratory experiments to improve the methods^[3]. A design is proposed on the computer, made and measured in the lab, and what is learned feeds the next round of software and designs; that loop is how the methods get better.

The lab organises its work into deep learning, enzymes, peptides, minibinders, molecular devices, drug delivery and nanomaterials^[3]. The areas differ in what the designed proteins are meant to do. Deep learning refers to models trained on protein data and used to predict structures and propose sequences. Enzymes are proteins that catalyse chemical reactions; peptides are short chains of amino acids; minibinders are small proteins designed to attach to a chosen target. Molecular devices and nanomaterials concern proteins assembled into larger working structures, and drug delivery concerns getting a therapeutic to where it is needed.

Place in the field

The 2024 prize recognised computational protein design as an area of chemistry^[1]. What Baker's group describes is not a single method but a continuing cycle between software and experiment^[3], carried out across a set of application areas that range from individual binding proteins to assembled materials^[3].