Navigation Links
MIT model could improve some drugs' effectiveness
Date:9/23/2007

CAMBRIDGE, MA--MIT researchers have developed a computer modeling approach that could improve a class of drugs based on antibodies, molecules key to the immune system. The model can predict structural changes in an antibody that will improve its effectiveness.

The team has already used the model to create a new version of cetuximab, a drug commonly used to treat colorectal cancer, that binds to its target with 10 times greater affinity than the original molecule.

The work, which will appear Sept. 23 in an advance publication of Nature Biotechnology, results from a collaboration using both laboratory experiments and computer simulations, between MIT Professors Dane Wittrup and Bruce Tidor.

New and better methods for improving antibody development represent critical technologies for medicine and biotechnology, says Wittrup, who holds appointments in MIT's Department of Biological Engineering and Department of Chemical Engineering. Tidor holds appointments in Biological Engineering and the Department of Electrical Engineering and Computer Science.

Antibodies, which are part of nature's own defense system against pathogens, are often used for diagnostics and therapeutics. Starting with a specific antibody, the MIT model looks at many possible amino-acid substitutions that could occur in the antibody. It then calculates which substitutions would result in a structure that would form a stronger interaction with the target.

Combining information about protein (antibody) structure with calculations that address the underlying atomic interactions allows us to make rational choices about which changes should be made to a protein to improve its function, said Shaun Lippow, lead author of the Nature Biotechnology paper.

Protein modeling can reduce the cost of developing antibody-based drugs, Lippow added, as well as enable the design of additional protein-based products such as enzymes for the conversion of biomass to fuel. Lippow conducted the research as part of his thesis work in chemical engineering at MIT, and is now a member of the protein engineering group at Codon Devices in Cambridge, Mass.

Making drugs out of huge, complicated molecules like antibodies is incredibly hard, said Janna Wehrle, who oversees computational biology grants at the National Institute of General Medical Sciences, which partially supported the research. Dr. Tidor's new computational method can predict which changes in an antibody will make it work better, allowing chemists to focus their efforts on the most promising candidates. This is a perfect example of how modern computing can be harnessed to speed up the development of new drugs.

Traditionally, researchers have developed antibody-based drugs using an evolutionary approach. They remove antibodies from mice and further evolve them in the laboratory, screening for improved efficacy. This can lead to improved binding affinities but the process is time-consuming, and it restricts the control that researchers have over the design of antibodies.

In contrast, the MIT computational approach can quickly calculate a huge number of possible antibody variants and conformations, and predict the molecules' binding affinity for their targets based on the interactions that occur between atoms.

Using the new approach, researchers can predict the effectiveness of mutations that might never arise by natural evolution.

The work demonstrates that by building on the physics underlying biological molecules, you can engineer improvements in a very precise way, said Tidor.

Expanding on that theme, Wittrup and Tidor also co-teach a class and are writing a textbook focusing on connecting fundamental molecular and cellular events to biological function through the use of mathematical models and computer simulations.

The team also used the model with an anti-lysozyme antibody called D44.1, and they were able to achieve a 140-fold improvement in its binding affinity. The authors expect the model will be useful with other antibodies as well.


'/>"/>

Contact: Elizabeth Thomson
thomson@mit.edu
617-258-5402
Massachusetts Institute of Technology
Source:Eurekalert

Related biology news :

1. Study Models Impact Of Anthrax Vaccine
2. Scientists identify new model Of NK cell development
3. Research Using Mouse Models Reveals A Novel Key Player In The Initiation Of Colon Cancer
4. Genrate: a generative model that finds and scores new genes and exons in genomic microarray data
5. Molecular models advance the fight against malaria
6. NYU and MSKCC research provides model for understanding chemically induced cancer initiation
7. Genetic therapy reverses nervous system damage in animal model of inherited human disease
8. Disease progression model of pancreatic cancer developed by Penn researchers
9. A new way to share models of biological systems
10. Understanding biases in epidemic models important when making public health predictions
11. Climate model links higher temperatures to prehistoric extinction
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/6/2017)... 2017  SomaLogic announced today that it has ... by iCarbonX, the China -based ... Digital Health Ecosystem that can define each person,s ... biological, behavioral and psychological data, the Internet and ... SomaLogic will provide proteomics data and applications expertise ...
(Date:12/22/2016)... 20, 2016  As part of its longstanding mission to ... genetics company, recently released its latest children,s book, titled ... focuses on the topics of inheritance and variation of traits ... taught in elementary school classrooms in the US. ... illustrator Ariana Killoran , whose previous book with 23andMe, ...
(Date:12/16/2016)... , Dec. 16, 2016   IdentyTechSolutions America ... management products and solutions and a cutting-edge manufacturer ... that it is offering seamless, integrated solutions that ... entrance products. The solutions provide IdentyTech,s customers with ... their facilities from crime and theft. ...
Breaking Biology News(10 mins):
(Date:1/19/2017)... 2017 BD (Becton, Dickinson and Company) (NYSE: ... will host a live webcast of its Annual Meeting of Shareholders ... The webcast can be accessed from the BD corporate website ... January 31, 2017. ... About BD BD is a global medical technology company ...
(Date:1/18/2017)... --  Parent Project Muscular Dystrophy (PPMD) , a nonprofit ... dystrophy (Duchenne) , today announced a $600,000 grant to ... (NJIT) and Talem Technologies (Talem) as part of the ... assist people living with Duchenne. PPMD is funding a ... computer, software, a force sensor and a motor – ...
(Date:1/18/2017)... Gainesville, FL (PRWEB) , ... January 18, 2017 ... ... muscle weakness and paralysis, today announced that it has submitted a 510(k) to ... stationary bikes that utilize MYOLYN’s patent-pending functional electrical stimulation (FES) technology. , ...
(Date:1/18/2017)... ... January 18, 2017 , ... Thirty-six startup companies in University ... the Pennsylvania Department of Community and Economic Development in 2016 as part of the ... the University City Keystone Innovation Zone and represent the highest number of awards to ...
Breaking Biology Technology: