Induced fit, conformational selection and independent dynamic segments: an extended view of binding events

TL;DR

This paper presents an extended conformational selection model for protein binding, emphasizing the roles of dynamic segments and the influence of cellular environments on binding mechanisms.

Contribution

It introduces a comprehensive model integrating various binding processes and highlights the importance of dynamic segments in conformational transitions and allosteric regulation.

Findings

Protein segments called 'discrete breathers' govern conformational changes.

Binding scenarios are influenced by bond types and partner differences.

Dynamic complexity affects aggregation and signaling in crowded environments.

Abstract

Single molecule and NMR measurements of protein dynamics increasingly uncover the complexity of binding scenarios. Here we describe an extended conformational selection model which embraces a repertoire of selection and adjustment processes. Induced fit can be viewed as a subset of this repertoire, whose contribution is affected by the bond-types stabilizing the interaction and the differences between the interacting partners. We argue that protein segments whose dynamics are distinct from the rest of the protein ('discrete breathers') can govern conformational transitions and allosteric propagation that accompany binding processes, and as such may be more sensitive to mutational events. Additionally, we highlight the dynamic complexity of binding scenarios as they relate to events such as aggregation and signalling, and the crowded cellular environment.