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High-affinity biomolecular interactions are modulated by low-affinity binders.

S Mukundan1, Girish Deshpande2,3, M S Madhusudhan4

  • 1Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pune, 411008, India.

NPJ Systems Biology and Applications
|August 10, 2024
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Summary
This summary is machine-generated.

Low-affinity binders, previously overlooked, can significantly impact high-affinity molecular interactions. This study introduces "herd regulation," demonstrating how these weaker binders influence interaction dynamics and cellular processes.

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Area of Science:

  • Molecular Biology
  • Systems Biology
  • Biophysics

Background:

  • Molecular interaction strength is quantified by dissociation constants (KD).
  • High-affinity interactions (KD ≤ 10-8 M) are typically studied for their binary on/off switch behavior.
  • Low-affinity binders (KD > 10-5 M) are often disregarded in cellular analyses despite their potential prevalence.

Purpose of the Study:

  • To investigate the influence of low-affinity binders on high-affinity molecular interactions.
  • To introduce and define the concept of 'herd regulation' by low-affinity binders.
  • To explore the implications of herd regulation in biological systems and propose experimental validation.

Main Methods:

  • Gillespie stochastic simulations to model molecular dynamics.
  • Continuous methods for analyzing interaction kinetics and steady states.
  • Case studies in Drosophila melanogaster sex determination and molecular threshold signaling systems.

Main Results:

  • Demonstrated that low-affinity binders can alter the kinetics and steady-state behavior of high-affinity interactions.
  • Introduced and defined the 'herd regulation' effect.
  • Evaluated the impact of herd regulation in specific biological contexts and proposed in vitro validation experiments.

Conclusions:

  • Low-affinity binders play a crucial role in modulating high-affinity interactions through 'herd regulation'.
  • This regulation mechanism may be significant in biological systems relying on molecular thresholds for homeostasis.
  • Further experimental validation is needed to confirm the widespread relevance of herd regulation in cellular processes.