Molecular Recognition between Cadherins Studied by a Coarse-Grained Model Interacting with a Coevolutionary...

Area of Science:

• Biophysics
• Computational Biology
• Structural Biology

Background:

• Cadherin dimerization is crucial for tissue development and implicated in diseases like cancer.
• Experimental methods often miss transient or minority conformations vital for molecular recognition.
• All-atom simulations are computationally prohibitive for exploring large-scale cadherin conformational dynamics.

Purpose of the Study:

• To develop and apply a computationally efficient model for studying cadherin multichain conformations.
• To identify sequence-specific dimeric conformations of cadherins.
• To complement experimental data with simulation insights into cadherin recognition.

Main Methods:

• Utilized a coarse-grained protein model in implicit solvent.
• Developed a novel interaction potential using coevolutionary information from cadherin alignments and a statistical potential.
• Explored the conformational space of multichain cadherin systems.

Main Results:

• Identified novel dimeric cadherin conformations.
• Demonstrated that these conformations are sequence-specific.
• Validated simulation findings against experimental data.

Conclusions:

• The developed coarse-grained model effectively explores cadherin conformational space.
• Sequence-specific dimeric conformations play a role in cadherin recognition.
• This approach provides a valuable tool for understanding cadherin function and dysfunction.