QnAs with David Baker

Abstract

DNA is often dubbed life’s instruction manual, but life-sustaining functions in all living cells are largely carried out by proteins, which are composed of varying combinations of 20 basic building blocks, called amino acids. Whether they are Lilliputian snippets a few amino acids long or molecular leviathans made of multiple large subunits, proteins in nature take their final 3D shapes, which are crucial for function, from the linear sequence of amino acids in their constituent chains. Researchers have attempted to tailor proteins for desired functions, but the efforts face a terrific challenge: predicting the folded 3D shape that any given engineered protein would assume inside living cells. The challenge, long known to protein scientists as the “folding problem,” is no more soluble for being familiar; it stems from the fact that interactions between individual amino acids and their environment are difficult to predict or preordain. However, the challenge has not stopped University of Washington protein biochemist David Baker, a member of the National Academy of Sciences, from trying. Nearly 25 years of steadfast efforts and a crowd-sourced army of worldwide volunteers have helped Baker make inroads into the folding problem. His group has designed from scratch proteins of exquisite structural complexity that might someday transform medicine and biotechnology. Baker recently presented his group’s advances at the Wyss Institute symposium on molecular robotics at Harvard Medical School. Baker shares his insights on de novo protein design with PNAS. David Baker. Image courtesy of Conrado Tapado (photographer). > PNAS:Protein engineering has made great strides in the past decade, and you have been at the forefront of exciting advances. How has the field evolved since the early days when random mutagenesis, …