This page describes some of my recent research.
FAQ - Text - Pictures.
To see all of my research please visit my lab webpages and list of publications.

All papers are from my lab, except for Clinical trials of designs in our papers, run by other groups.

So, what have you done recently?

We developed computational structure-based protein design algorithms that could revolutionize therapeutic treatment. Our algorithms should enable the design of proteins and other molecules to act on today's undruggable proteins and tomorrow's drug resistant diseases.

We developed novel protein design algorithms and open-source software, and used them to:

Ok, cool. Can you give me some technical details?


Neat! Is that all?

No, lots of other cool stuff is below, and/or in my papers and books.

How about some pictures?

Sure, please see below.

Cover Articles

Recent papers (See all)

Drug Design

Broad spectrum inhibitors targeting methicillin-resistant clinical isolates of Staph. aureus

ACS Infectious Diseases (2019)

Combatting Leukemia:
RUNX1 and CBFβ Interaction Interupted.
Chemistry & Biology (2007).

Protein Structures Gallery

List all structures (NCBI)

Structure of a membrane-associated MPER trimer from HIV-1 gp41

PDB id: 2m7w.

Solution structure of FF Domain 2 of human transcription elongation factor CA150.
PDB ID: 2KIQ (J. Biomol. NMR 2009)

Structure of Dihydrofolate Reductase-Thymidylate Synthase from Cryptosporidium hominis.
PDB ID: 1QZF (J. Biol. Chem.)

Complete ensemble of NMR structures of the unphosphorylated human cardiac phospholamban pentamer. PDB ID: 2HYN (Proteins, 2006)

Nanoscience and Microelectromechanical Systems

Independent Control of Stress-engineered MEMS Microrobots
Robotics: Systems and Science (2012)

Planar Microassembly by Parallel Actuation
of MEMS Microrobots.
Journal of Microelectromechanical Systems (2008).

Neuroscience, Microtechnology, and Nanotechnology

Auditory synapses to song premotor neurons
eLife (2014)

Intracellular Neural Recording with
Pure Carbon Nanotube Probes

PLoS (2013).

Microassembly by Microrobots

International Journal of Robotics Research (2013)

Carbon nanotube-based probes for scanning microscopy and neural recording

Journal of Applied Physics (2012).

Protein Design

Computational Design of a PDZ Domain Peptide Inhibitor that Rescues CFTR Activity

PLoS Computational Biology (April, 2012).

Protein Design using Continuous Rotamers

PLoS Computational Biology (Jan, 2012).

The Role of Local Backrub Motions in Evolved and Designed Mutations

PLoS Computational Biology (August, 2012).

Cover Article

Protein loop closure using orientational
restraints from NMR data.
Proteins (2011)

Protein Design

DEEPer: A provable protein design algorithm with continuous sidechain and backbone flexibility

Proteins (July, 2012).

Design of Epitope-Specific Probes for Sera Analysis and Antibody Isolation

Retrovirology (2012).

OSPREY: Protein Design with Ensembles, Flexibility, and Provable Algorithms

Methods in Enzymology (2013)

Structure of an HIV Neutralizing Antibody Target: A Lipid Bound gp41 Envelope Membrane Proximal Region Trimer.
PNAS (2014)

Cover Article
Systematic solution to homoöligomeric structures determined by NMR
Proteins (2015)

Algorithms for protein design
Curr Opin Struct Biol. (2016)

An enhanced anti-HIV broadly neutralizing antibody
Journal of Virology (2014)

CATS (Coordinates of Atoms by Taylor Series): Protein design with backbone flexibility in all locally feasible directions

ISMB & Bioinformatics (2017)

Podcast: Spotify, Apple Podcast (2021)

Featured Research (See all)

Safety and immunogenicity of HIV-1 vaccine Trimer 4571 (BG505 DS-SOSIP.664), from our Nature paper, was assessed in clinical trials. Here is one of several:
Safety and immunogenicity of an HIV-1 prefusion-stabilized envelope trimer (Trimer 4571) vaccine in healthy adults: A first-in-human open-label, randomized, dose-escalation, phase 1 clinical trial. The Lancet Clinical Medicine (2022)

Nature Structural & Molecular Biology
Structure and conformational fixation
of mature ligand-free HIV Envelope Trimer

Other Clinical Trials (See all 20)

Comment in The Lancet
A designed antibody from our Jour. Virology paper is currently in 20 clinical trials. Here are two: Identifier: NCT03015181
Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC07-523LS, Administered Intravenously or Subcutaneously
National Institutes of Health Clinical Center (2017)

Phase I study results in The Lancet. Identifier: NCT03387150
Evaluating the Safety and Serum Concentrations of a Human Monoclonal Antibody, VRC07-523LS, Administered in Multiple Doses and Routes

National Institutes of Health Clinical Center (2017)

See all 20 clinical trials

Chiral evasion and stereospecific antifolate resistance in Staph. aureus

PLoS Computational Biology (2022)
Cover article

Protein Design

Predicting Cancer Resistance Mutations by Pareto Optimization Over Multistate Protein Design

RECOMB (2022), In Press.

Computational design of a tight binder to KRas, an “undruggable” cancer target

PLoS Computational Biology 2020.

Predicting Resistance Mutations
using Protein Design Algorithms.
PNAS (2010).

Protein Design Algorithms Predict Viable
Resistance to an Experimental Antifolate
PNAS (2015)

Computational Structure-Based Redesign of Enzyme Activity.
PNAS (2009).


K-12: Developing a Fluoride Riboswitch

East Chapel Hill High School iGEM Team (2017) &
Chloramphenicol acetyltransferase operon for an improved Fluoride Riboswitch as a Technology to Combat Excess Fluoride in Water

Energy landscapes of inhibitors binding to
Cystic Fibrosis transmembrane conductance regulator
(CFTR)-Associated Ligand

Journal of Physical Chemistry B (2019)
local PDF

Broad spectrum inhibitors targeting methicillin-resistant clinical isolates of Staph. aureus

ACS Infectious Diseases (2019)

Osprey has a Python interface and integrated GPU support

A convenient Python scripting interface and support for GPU acceleration allows designs to be completed far more quickly and easily (2020).

Continuous interdomain orientation distributions reveal components of binding thermodynamics

Journal of Molecular Biology (2018)

Osprey 3.0


Open Source Protein REdesign for You, with Powerful New Features
Journal of Computational Chemistry (2018).
Cover article

[PDF, Accepted MS, Download Code]

Recent Papers (See all)

Sublinear-Time Protein Design Algorithm to Optimize Binding Affinity and Stability over Large Sequence Spaces

JCB (2018)