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Related Concept Videos

Three-Dimensional Force System01:30

Three-Dimensional Force System

In mechanical engineering, a three-dimensional force system is a system of forces acting in three dimensions, with forces applied along the x, y, and z coordinate axes. The three-dimensional force system is an important concept in mechanical engineering, as it allows engineers to understand and analyze the behavior of objects and structures in three dimensions. By understanding the forces acting on a system, engineers can design more efficient and effective mechanical systems that can withstand...
Three-Dimensional Force System:Problem Solving01:30

Three-Dimensional Force System:Problem Solving

A three-dimensional force system refers to a scenario in which three forces act simultaneously in three different directions. This type of problem is commonly encountered in physics and engineering, where it is necessary to calculate the resultant force on the system, which can then be used to predict or analyze the behavior of the object or structure under consideration.
To solve a three-dimensional force system, first resolve each force into its respective scalar components. Do this using...
Equations of Equilibrium in Three Dimensions01:30

Equations of Equilibrium in Three Dimensions

When analyzing structures or systems at rest, it is necessary to ensure they are in equilibrium. This is where the vector and scalar equations of equilibrium come into play. These equations are crucial in ensuring a structure is stable and will not collapse or fall apart. The vector and scalar equations of equilibrium provide a framework for analyzing the forces acting on a body.
According to the vector equations of equilibrium, the vector sum of all the external forces acting on a body must...
Support Reactions in Three Dimensions01:27

Support Reactions in Three Dimensions

Support reactions in three dimensions help maintain the stability and equilibrium of various structures and systems. These reactions prevent the system from translating and rotating, ensuring the design can withstand external forces and perform its intended function efficiently and safely. Some of the supports providing support reactions in three dimensions are discussed below:
Ball and Socket Joint is one of the supports allowing free rotation about any axis. This freedom of rotation is...
Method of Joints: Problem Solving II01:30

Method of Joints: Problem Solving II

Consider a truss structure with frictionless joints fixed to a wall and roller support. If a force of 150 N is applied to joint A, the forces in each member of the truss can be determined using the method of joints.
Relative Motion Analysis using Rotating Axes-Problem Solving01:29

Relative Motion Analysis using Rotating Axes-Problem Solving

Consider a crane whose telescopic boom rotates with an angular velocity of 0.04 rad/s and angular acceleration of 0.02 rad/s2. Along with the rotation, the boom also extends linearly with a uniform speed of 5 m/s. The extension of the boom is measured at point D, which is measured with respect to the fixed point C on the other end of the boom. For the given instant, the distance between points C and D is 60 meters.
Here, in order to determine the magnitude of velocity and acceleration for point...

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The Importance of Correct Protein Concentration for Kinetics and Affinity Determination in Structure-function Analysis
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Quantitative analysis of ternary complex kinetics by a surface immobilization method.

Xiaohan Mai1, Yang Luo2, Ruoxin Fang3

  • 1Shanghai Engineering Research Center of Ultra-precision Optical Manufacturing, Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education), College of Future Information Technology, Fudan University, Shanghai, 200433, China; Quzhou Fudan Institute, 108 Minjiang Avenue, Kecheng District, Quzhou, Zhejiang Province, China.

Biochemical and Biophysical Research Communications
|March 7, 2026
PubMed
Summary

Bifunctional molecules enable targeted protein degradation by forming ternary complexes. This study presents a framework combining modeling and experiments to accurately characterize these complexes, aiding in the development of potent therapeutics.

Keywords:
Cooperativity factorHook effectOblique-incidence reflectivity differenceTarget protein degradationTernary complex kinetics

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Area of Science:

  • Biochemistry
  • Chemical Biology
  • Drug Discovery

Background:

  • Targeted protein degradation using bifunctional molecules is a key therapeutic strategy.
  • Efficient degradation hinges on the formation of a ternary complex involving the target protein, E3 ligase, and the bifunctional molecule.
  • Quantifying the kinetics of ternary complex formation is crucial for optimizing degrader efficacy.

Purpose of the Study:

  • To establish an integrated framework for reliable kinetic characterization of ternary complexes.
  • To demonstrate how theoretical modeling and experimental validation can be combined for accurate kinetic analysis.
  • To provide a systematic methodology for quantifying ternary complex kinetics and guiding degrader optimization.

Main Methods:

  • Development of a theoretical modeling framework for kinetic characterization.
  • Experimental validation using component immobilization and calibrated concentrations of pre-formed binary complexes.
  • Application to the CRBN/ARV-825/BRD4 system to assess cooperativity and degradation potency.

Main Results:

  • Binary binding parameters effectively guide experimental design for accurate measurements.
  • The CRBN/ARV-825/BRD4 system exhibits strong positive cooperativity (α = 175).
  • High cooperativity correlates with exceptional protein degradation potency.

Conclusions:

  • The integrated framework provides a reliable method for quantifying ternary complex kinetics.
  • This approach enables kinetic-guided design for rational optimization of targeted protein degraders.
  • The study offers a robust platform for advancing therapeutic strategies based on targeted protein degradation.