Related Experiment Video
Updated: Feb 2, 2026
13:58
Peptide:MHC Tetramer-based Enrichment of Epitope-specific T cells
Published on: October 22, 2012
18.7K
Computational Design of Epitope-Specific Functional Antibodies
Guy Nimrod1, Sharon Fischman1, Mark Austin2
1Biolojic Design, Ltd., 12 Hamada Street, Rehovot 7670314, Israel.
Cell Reports
|November 22, 2018
Summary
We developed a novel computational method for designing functional antibodies targeting specific protein interactions. This approach, using machine learning and structural analysis, successfully created an antibody against interleukin-17A (IL-17A), demonstrating its potential for drug discovery.
Area of Science:
- * Computational biology and structural immunology.
- * Protein engineering and antibody design.
- * Machine learning applications in biophysics.
Background:
- * The primary objective in protein design is to engineer novel biological functions.
- * Designing functional antibodies typically requires detailed structural information of the target and antibody complex.
- * Existing methods face challenges due to the complexity of protein interactions and the need for high-resolution structural data.
Purpose of the Study:
- * To present a computational strategy for designing functional antibodies by focusing on key interaction sites (epitopes).
- * To demonstrate the efficacy of this approach by designing an antibody against the pro-inflammatory cytokine interleukin-17A (IL-17A).
- * To validate a method that minimizes reliance on pre-existing high-quality structural models.
Main Methods:
- * Integration of large-scale statistical analysis with multiple protein structural models.
- * Application of machine learning algorithms to predict critical residue-residue contacts within the antibody-epitope interface.
- * Iterative design and experimental validation using X-ray crystallography and cell-based assays.
Main Results:
- * Successful design and synthesis of a functional antibody targeting the specific epitope of interleukin-17A (IL-17A).
- * X-ray crystallography confirmed the designed antibody's binding to the target epitope, mediated by predicted residue contacts.
- * Cell-based assays validated the antibody's biological activity in neutralizing IL-17A's pro-inflammatory effects.
Conclusions:
- * The proposed computational approach enables the design of functional antibodies without requiring a high-resolution 3D model of the target complex.
- * This method significantly advances antibody design by overcoming major hurdles in structural biology and drug discovery.
- * The strategy holds promise for accelerating the development of novel therapeutics and biologics.
Related Concept Videos
01:25Design Example: Traverse Angle Computations
341
Traverse angle computations are a critical component of surveying, used to compute the internal angles within a closed traverse. A traverse consists of a series of connected lines forming a closed loop, often used for land boundary delineation or mapping. Calculating the internal angles ensures accuracy in the traverse geometry and is essential for checking survey data integrity.The process begins with known azimuths and bearings of the traverse sides. Internal angles at each vertex are...
341
02:01Group Design
10.5K
The most basic experimental design involves two groups: the experimental group and the control group. The two groups are designed to be the same except for one difference— experimental manipulation. The experimental group gets the experimental manipulation—that is, the treatment or variable being tested—and the control group does not. Since experimental manipulation is the only difference between the experimental and control groups, we can be sure that any differences between...
10.5K
01:10Antibody Structure
65.5K
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
65.5K
02:01Factorial Design
13.8K
Factorial Analysis is an experimental design that applies Analysis of Variance (ANOVA) statistical procedures to examine a change in a dependent variable due to more than one independent variable, also known as factors. Changes in worker productivity can be reasoned, for example, to be influenced by salary and other conditions, such as skill level. One way to test this hypothesis is by categorizing salary into three levels (low, moderate, and high) and skills sets into two levels (entry level...
13.8K
01:10Computed Tomography
8.3K
Tomography refers to imaging by sections. Computed tomography (CT) is a non-invasive imaging technique that uses computers to analyze several cross-sectional X-rays to reveal minute details about structures in the body.
The technique was invented in the 1970s and is based on the principle that as X-rays pass through the body, they are absorbed or reflected at different levels. In the technique, a patient lies on a motorized platform while a computerized axial tomography (CAT) scanner rotates...
The technique was invented in the 1970s and is based on the principle that as X-rays pass through the body, they are absorbed or reflected at different levels. In the technique, a patient lies on a motorized platform while a computerized axial tomography (CAT) scanner rotates...
8.3K
01:25Design Example: Designing a Residential Plumbing System
1.1K
The design of residential plumbing systems requires carefully evaluating water demand, flow rates, and pressure dynamics to ensure both efficiency and reliability. The nature of water flow within pipes is defined by its Reynolds number, which classifies flow as either laminar (smooth) or turbulent.
1.1K