T. Kortemme

An integrative approach to protein sequence design through multiobjective optimization

This paper introduces an evolutionary multiobjective optimization framework for protein sequence design, combining AlphaFold2 and ProteinMPNN to improve sequence recovery in complex design problems.

Targeting high-risk multiple myeloma genotypes with optimized anti-CD70 CAR-T cells

Structure-optimized CD27-based CAR-T cells targeting CD70 show >80-fold improved expansion in vivo and offer a potential therapy for high-risk multiple myeloma patients.

Structure-conditioned masked language models for protein sequence design generalize beyond the native sequence space

This paper introduces Frame2seq, a structure-conditioned masked language model for protein sequence design that generates novel, stable proteins with low sequence identity to native sequences.

Computational pipeline provides mechanistic understanding of Omicron variant of concern neutralizing engineered ACE2 receptor traps

The paper develops a computational pipeline combining Rosetta and cryo-EM to analyze ACE2 receptor traps' binding to SARS-CoV-2 variants, showing high affinity and neutralization capabilities against Omicron and Delta.

A complete allosteric map of a GTPase switch in its native network

The paper systematically identifies new allosteric regulatory sites in Gsp1/Ran by mutational scanning, revealing that many deleterious mutations affect function outside the active site through allosteric coupling.

Ligand-induced changes in dynamics mediate long-range allostery in the lac repressor

This study uses HDX/MS to show ligand-induced changes in dynamics mediate long-range allostery in the lac repressor, revealing flexibility differences in secondary structures across functional states.

Accurately positioning functional residues with robotics-inspired computational protein design

This paper introduces two computational methods for accurately positioning functional residues in proteins and validates them by redesigning enzyme active sites.

De novo protein fold families expand the designable ligand binding site space

The paper constructs a library of ligand binding sites and shows de novo protein scaffolds expand the designable ligand binding site space compared to natural scaffolds.

Expanding the space of protein geometries by computational design of de novo fold families

A computational method expands the structure space of designer proteins by systematically sampling loop-helix-loop geometries.

Modulating the cellular context broadly reshapes the mutational landscape of a model enzyme

The paper shows that the absence of the protease Lon in E. coli reshapes the mutational landscape of DHFR, increasing the proportion of advantageous mutations.

Comparison of Rosetta flexible-backbone computational protein design methods on binding interactions

This study compares flexible-backbone computational protein design methods in Rosetta, finding that CoupledMoves better recaptures observed sequence profiles for binding interactions than BackrubEnsemble and FastDesign.

Computational design of a modular protein sense/response system

This paper designs modular protein sensors that respond to specific small molecule inputs using a computational strategy.

Quantitative mapping of protein-peptide affinity landscapes using spectrally encoded beads

This study introduces MRBLE-pep, a method to quantify protein-peptide affinity landscapes, revealing critical factors influencing binding and identifying potential therapeutic peptides.

Flex ddG: Rosetta ensemble-based estimation of changes in protein-protein binding affinity upon mutation

The paper introduces flex ddG, a method using Rosetta to estimate binding affinity changes upon mutation by sampling conformational diversity, and shows it outperforms existing methods in several mutation types.

The Rosetta all-atom energy function for macromolecular modeling and design

The paper explains the Rosetta all-atom energy function, its mathematical models, and its application to biomolecular modeling and design, including new capabilities for membrane proteins and other macromolecules.