##  [Predictive Design of Biologics](/predictive-design-biologics) 

# *Predictive Design of Biologics*





 



  

    

 



 

 



 

 



 

 

 

## Rapid Computational Design & Experimental Validation of Antibodies

LLNL biologists, computer scientists and engineers are developing a machine-learning enabled computational/experimental framework that enables unprecedented acceleration of the drug development process.

Our platform integrates world-class high-performance computing and simulation, machine learning, structural bioinformatics, and multi-objective optimization to perform in silico antibody and antigen design and optimization. These designs are then experimentally validated at LLNL and at our partner facilities, and results are either pursed as candidate medical countermeasures (MCMs) or provided as critical feedback for computational redesign.

 ![Guide Process chart](https://engineering.llnl.gov/sites/engineering/files/2022-10/guide-photo.png "Guide Process chart")

We are partnering with academia, and industry to further develop and demonstrate this capability. When fully implemented our system will enable both a proactive and rapid reactive approach for designing MCMs

If you are interested in joining our team or have questions, please contact us at CPDB \[at\] llnl.gov (CPDB\[at\]llnl\[dot\]gov)



 



 

 



 

 



 

 

 



## Research Highlights



 



 

 



 

 



 

 

 

  ![image of covid virus](/sites/engineering/files/styles/orig/public/2022-10/covid2.jpg?itok=pEvOOvLZ)

    

 



 

 



 

[**Computationally restoring the potency of a clinical antibody against SARS-CoV-2 Omicron subvariants**](https://www.biorxiv.org/content/10.1101/2022.10.21.513237v2)

With the emergence of the SARS-CoV-2 Omicron variant in late 2021, many clinically used antibody drug products lost potency, including Evusheld and its constituent, cilgavimab. Rapidly modifying such high-value antibodies with a known clinical profile to restore efficacy against emerging variants is a compelling mitigation strategy. We sought to redesign COV2-2130 to rescue in vivo efficacy against Omicron BA.1 and BA.1.1 strains while maintaining efficacy against the contemporaneously dominant Delta variant. Here we show that our computationally redesigned antibody, 2130-1-0114-112, achieves this objective, simultaneously increases neutralization potency against Delta and many variants of concern that subsequently emerged, and provides protection in vivo against the strains tested.



 



 

 



 

 



 

 

 

  ![A depiction of the mutation position of  AbBERT: Learning Antibody Humanness Via Masked Language Modeling](/sites/engineering/files/styles/orig/public/2022-10/abbert-graphic.jpg?itok=VGzVgJdi)

    

 



 

 



 

[**AbBERT: Learning Antibody Humanness Via Masked Language Modeling**](https://www.biorxiv.org/content/10.1101/2022.08.02.502236v1)

One component of our computational pipeline is a model to understand the degree of similarity of novel, engineered antibody sequences to typical human antibody sequences. Accurate understanding of the degree of humanness can help reduce or manage the risk of failure modes such as immunogenicity or poor manufacturability. AbBERT was developed to fill this need as a transformer-based language model derived from ProtBert, which was trained on up to 20 million unpaired sequences from the Observed Antibody Space database.

We validated AbBERT using a novel “multi-mask'' scoring procedure to demonstrate high accuracy in predicting antibody complementary determining regions—including the challenging hypervariable H3 region. We then demonstrated several uses of AbBERT on downstream antibody design and prediction tasks. AbBERT enhances in silico antibody optimization via deep reinforcement learning by utilizing its learned embeddings as additional observations during optimization.



 



 

 



 

 



 

 

 

## Other Research Manuscripts



 



 

 



 

 



 

 

 

- [SARS-COV-2 Omicron variant predicted to exhibit higher affinity to ACE-2 receptor and lower affinity to a large range of neutralizing antibodies, using a rapid computational platform](https://www.biorxiv.org/content/10.1101/2021.12.16.472843v2)
- [Language model-accelerated deep symbolic optimization](https://link.springer.com/article/10.1007/s00521-023-08802-8)
- [Learning Regions of Interest for Bayesian Optimization with Adaptive Level-Set Estimation](https://arxiv.org/abs/2307.13371)
- [Large-scale application of free energy perturbation calculations for antibody design](https://www.nature.com/articles/s41598-022-14443-z)
- [Learning Regions of Interest for Bayesian Optimization with Adaptive Level-Set Estimation](https://openreview.net/pdf?id=6aB43K50T0)



 



 

 



 

 



 

 

 

## Join Our Team



 



 

 



 

 



 

 

 

 ![Workers performing a variety of jobs](https://engineering.llnl.gov/sites/engineering/files/2022-10/triptych-opt.jpg "Workers performing a variety of jobs")

We have career opportunities to develop a next generation computational antibody and antigen design platform driven by simulation and machine learning models trained on large experimental datasets.

- [High Throughput Protein Display Platform Scientist](https://www.smartrecruiters.com/app/employee-portal/5f3a70052f26b020bfe81917/jobs/36b2e92c-cee4-4a3a-858e-49593f79e900)

Lawrence Livermore National Laboratory has been [ranked among the top 10 employers](https://www.llnl.gov/news/forbes-llnl-among-america%E2%80%99s-best-employers) in the San Francisco Bay Area by Forbes Magazine, won multiple [Glassdoor Best Places to Work awards](https://www.llnl.gov/news/lawrence-livermore-makes-glassdoors-2022-best-places-work-list), and is among the top 12 in government services nationwide. The Laboratory offers employees outstanding careers with a first-class benefits package in a beautiful location. See our Careers page for more information about our culture, the benefits and perks, our history, and job opportunities.



 



 

 



 

 



 

 

 

## Our Leadership



 



 

 



 

 



 

 

 

 ![Photo of Dan Faissol](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-faissol-dan.jpg "Photo of Dan Faissol")

**[Dan Faissol, PhD](https://people.llnl.gov/faissol1)**  
Principal Investigator



 ![Photo of Shankar Sundaram](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-sundaram-shankar.jpg "Photo of Shankar Sundaram")

**[Shankar Sundaram, PhD](https://people.llnl.gov/sundaram1)**  
Program Executive



 ![Photo of Tom Bates](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-bates-tom.jpg "Photo of Tom Bates")

**[Tom Bates, PhD](https://people.llnl.gov/bates13)**  
Program Deputy



 ![Photo of John Hernandez](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-john-hernandez.jpg "Photo of John Hernandez")

**[John Hernandez](https://people.llnl.gov/hernandez4)**  
Business Project Manager





 ![Photo of Kate Arrildt](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-arrildt-kate.jpg "Photo of Kate Arrildt")

**Kate Arrildt, PhD**  
Virology, Vaccinology



 ![Photo of Thomas Bunt](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-bunt-thomas.jpg "Photo of Thomas Bunt")

**Thomas Bunt**  
Rapid Response Laboratory Lead



 ![Photo of Barry Chen](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-barry-chen.jpg "Photo of Barry Chen")

**Barry Chen**, **PhD**  
Language Modeling Lead



 ![Photo of Simone Conti](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-simone-conti_.jpg "Photo of Simone Conti")

**Simone Conti**, **PhD**  
Molecular Dynamics Simulations





 ![Photo of Jie Deng](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-jie-deng.jpg "Photo of Jie Deng")

**Jie Deng**  
Software and Data Architect



 ![Photo of Tom Desautels](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-desautels-tom.jpg "Photo of Tom Desautels")

**Tom Desautels, PhD**  
Multi-fidelity Simulation and Machine Learning for Efficacy Prediction



 ![Photo of John Goforth](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-goforth-john.jpg "Photo of John Goforth")

**John Goforth**  
Software Development Lead



 ![Photo of Mikel Larma](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-landajuela-mikel.jpg "Photo of Mikel Larma")

**Mikel Landajuela**, **PhD**  
Optimization Lead





 ![Photo of Ed Lau](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-lau-ed.jpg "Photo of Ed Lau")

**Ed Lau, PhD**  
Molecular Dynamics Simulation



 ![Photo of Ed Saada](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-saada-ed.jpg "Photo of Ed Saada")

**Ed Saada, PhD**  
Pathogen Interactions and Medical Countermeasures



 ![Photo of Ana Paula Sales](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-ana-paula-sales.jpg "Photo of Ana Paula Sales")

**Ana Paula Sales**, **PhD**  
Developability Prediction Lead



 ![Photo of Brent Segelke](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-segelke-brent.jpg "Photo of Brent Segelke")

**Brent Segelke, PhD**  
Structural Biologist, Protein Biochemist





 ![Photo of Adam Zelma](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-zelma-adam.jpg "Photo of Adam Zelma")

**Adam Zemla, PhD**  
Protein Structure Bioinformatics



 ![Photo of Fangqiang Zhu](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-zhu-fangqiang.jpg "Photo of Fangqiang Zhu")

**Fangqiang Zhu, PhD**  
Molecular Dynamics Simulation, Structural Antibody Modeling







 



 

 



 

 



 

 

 

## The Team



 



 

 



 

 



 

 

 

 ![Photo of Aram Avila-Herrera](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-aram-avila-herrera.jpg "Photo of Aram Avila-Herrera")

**Aram Avila-Herrera**  
 Bioinformatics Software Developer

 

 ![Photo of Drew Bennett](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-bennett-z.jpg "Photo of Drew Bennett")

**Drew Bennett, PhD**  
 Molecular Dynamics Simulation, Multi-scale Modeling

 

 ![Photo of Jose Cadena Pico](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-cadena-pico-jose.jpg "Photo of Jose Cadena Pico")

**Jose Cadena Pico, PhD**  
 Machine Learning

 

 ![Photo of Ippolito Imani Caradonna](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-ippolito-imani-caradonna.jpg "Photo of Ippolito Imani Caradonna")

**Ippolito Imani Caradonna**  
 Automation Expert

 

 

 ![Photo of Rudrasis Chakraborty](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-rudrasis-chakraborty.jpg "Photo of Rudrasis Chakraborty")

**Rudrasis Chakraborty**  
 Researcher

 

 ![Photo of Matt Coleman](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-coleman-matt.jpg "Photo of Matt Coleman")

**Matt Coleman, PhD**  
 Vaccinologist, Biochemical Engineer

 

 ![Photo of Zachary Cosenza](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-zachary-cosenza.jpg "Photo of Zachary Cosenza")

**Zachary Cosenza**  
 Bayesian Modeling, Multi-task Learning

 

 ![Photo of Aneesha Devulapally](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-aneesha-devulapally.jpg "Photo of Aneesha Devulapally")

**Aneesha Devulapally**  
 ChemBio Data Scientist

 

 

 ![Photo of Jeff Drocco](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-drocco-jeff.jpg "Photo of Jeff Drocco")

**Jeff Drocco, PhD**  
 Bioinformatics

 

 ![Photo of Andre Goncalves](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-goncalves-andre.jpg "Photo of Andre Goncalves")

**Andre Goncalves, PhD**  
 Machine Learning, Multi-task Learning, Multi-objective Optimization

 

 ![Photo of Emilia Gzesiak](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-grzesiak-emilia.jpg "Photo of Emilia Gzesiak")

**Emilia Grzesiak**  
 Biostatics and Data Science, Software Development

 

 ![Photo of Rebecca Haluska](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-haluska-rebecca.jpg "Photo of Rebecca Haluska")

**Rebecca Haluska**  
 Software Development and Database Engineering

 

 

 ![Photo of Conor Hayes, PhD](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-conor-hayes.jpg "Photo of Conor Hayes, PhD")

**Conor Hayes, PhD**  
 Reinforcement Learning, Machine Learning

 

 ![Photo of Matthew Jemielita](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-matthew-jemielita.jpg "Photo of Matthew Jemielita")

**Matthew Jemielita**   
 Assay Dev Lead

 

 ![Photo of Piyush Karande, PhD](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-piyush-karande.jpg "Photo of Piyush Karande, PhD")

**Piyush Karande, PhD**  
 Deep Learning

 

 ![Photo of Tek Huang Lee](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-hyung-lee-tek.jpg "Photo of Tek Huang Lee")

**Tek Hyung Lee, PhD**  
 Synthetic and Systems Biologist and Microbial Engineer

 

 

 ![Photo of Leno Da Silva](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-da-silva-leno.jpg "Photo of Leno Da Silva")

**Leno De Silva, PhD**  
 Deep Reinforcement Learning

 

 ![Photo of Tavish McDonald](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-tavish-mcdonald_.jpg "Photo of Tavish McDonald")

**Tavish McDonald**  
 Machine Learning, Language Modeling

 

 ![Photo of Yamen Mubarka](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-yamen-mubarka.jpg "Photo of Yamen Mubarka")

**Yamen Mubarka**  
 Deep Learning

 

 ![Photo of Nate Mundhenk](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-mundhenk-nate.jpg "Photo of Nate Mundhenk")

**Nate Mundhenk, PhD**  
 Deep learning, Convolutional Neural Networks

 

 

 ![Photo of Rami Musharrafieh](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-rami-musharrafieh.jpg "Photo of Rami Musharrafieh")

**Rami Musharrafieh**  
 Vaccines Lead

 

 ![Photo of Christine Ocampo](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-christine-ocampo.jpg "Photo of Christine Ocampo")

**Christine Ocampo**  
 Operation Administrator

 

 ![Photo of Kim Phan](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-kim-phan.jpg "Photo of Kim Phan")

**Kim Phan**  
 Administrative Specialist

 

 ![Photo of Hiranmayi Ranganathan, PhD](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-hiranmayi-ranganathan.jpg "Photo of Hiranmayi Ranganathan, PhD")

**Hiranmayi Ranganathan, PhD**  
 Deep Active Learning, Machine Learning

 

 

 ![Photo of Tiffany Reck ](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-tiffany-reck.jpg "Photo of Tiffany Reck ")

**Tiffany Reck**   
 Administrative Specialist

 

 ![Photo of Dante Ricci](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-ricci-dante.jpg "Photo of Dante Ricci")

**Dante Ricci, PhD**  
 Molecular Genetics, Systems Biology

 

 ![Photo of Natalie Rowland](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-natalie-rowland.jpg "Photo of Natalie Rowland")

**Natalie Rowland**  
 Administrative Specialist

 

 ![Photo of Bonnee Rubinfeld](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-rubinfeld-bonnee.jpg "Photo of Bonnee Rubinfeld")

**Bonnee Rubinfeld**  
 Cellular, Molecular, Micro-biologist/Biochemist

 

 

 ![Photo of Mary Silva](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-silva-mary.jpg "Photo of Mary Silva")

**Mary Silva**  
 Bayesian Statistics and Data Science

 

 ![Photo of Cheryl Strout](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-strout-cheryl.jpg "Photo of Cheryl Strout")

**Cheryl Strout**  
 Biochemical and Analytical Scientist

 

 ![Photo of Gareth Trubl, PhD](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-gareth-trubl.jpg "Photo of Gareth Trubl, PhD")

**Gareth Trubl, PhD**  
 Viral and Microbial Ecologist

 

 ![Photo of Camilo Valdes](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-valdes-camilo.jpg "Photo of Camilo Valdes")

**Camilo Valdes, PhD**  
 Bioinformatics

 

 

 ![Photo of Denis Vashchenko](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-vashchenko-denis.jpg "Photo of Denis Vashchenko")

**Denis Vashchenko**  
 Deep Learning Language Modeling, Software Development

 

 ![Photo of Yaqing Wang, PhD](https://engineering.llnl.gov/sites/engineering/files/2023-10/eng-bio-yaqing-wang.jpg "Photo of Yaqing Wang, PhD")

**Yaqing Wang, PhD**  
 Structural Biologist, Molecular Biophysicist

 

 ![Photo of Dina Weilhammer](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-weilhammer-dana.jpg "Photo of Dina Weilhammer")

**Dina Weilhammer, PhD**  
 Immunologist, Virologist

 

 ![Photo of Tracy Weisenberger](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-weisenberger-tracy.jpg "Photo of Tracy Weisenberger")

**Tracy Weisenberger**  
 Cellular, Molecular, and Viral Biologist

 

 

 ![Photo of Boya Zhang](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-bio-zhang-boya.jpg "Photo of Boya Zhang")

**Boya Zhang, PhD**  
 Machine learning, surrogate-based modeling

 

 



 



 

 



 

 



 

 

 

  ![placeholder -woman in white](/sites/engineering/files/styles/orig/public/2022-10/432092973.jpg?itok=yxYdLPXO)

 

 ## Interested in joining the cutting edge of computational design and bioengineering?

CPDB \[at\] llnl.gov (Contact us )



   

 



 



 

 



 

 



 

 

 

Predictive Design of Biologics is a collaborative effort spearheaded by two Lawrence Livermore National Laboratory organizations:

 

[ ![LLNL Engineering logo](https://engineering.llnl.gov/sites/engineering/files/2022-10/eng-logo-horiz.png "LLNL Engineering logo")](https://engineering.llnl.gov)

[ ![gs-logo-primary-full-color-onclear.png](https://engineering.llnl.gov/sites/engineering/files/2022-10/gs-logo-primary-full-color-onclear.png "gs-logo-primary-full-color-onclear.png")](https://gs.llnl.gov)