Energy landscape views for interplays among folding, binding, and allostery of calmodulin domains

• DOI: 10.1073/pnas.1402768111
• Publication Date: 2014-07-08T03:01:33Z
• Authors: Wenfei Li; Wei Wang; Shoji Takada
• Keywords: Models, Molecular; 0301 basic medicine; Protein Denaturation; Protein Folding; Binding Sites; Temperature; 01 natural sciences; Protein Structure, Tertiary; 03 medical and health sciences; Allosteric Regulation; Calmodulin; 0103 physical sciences; Thermodynamics; Calcium; Computer Simulation; Stress, Mechanical; Protein Binding

Significance Protein dynamics can conceptually be classified into three factors: folding, conformational transitions, and chemical events. Although couplings between every two of these factors have been well studied, explicit coupling among the three factors has not been examined due to its difficulty in direct experimental measurements. Toward this direction, calmodulin is a suitable model system. Here, constructing a computational model that integrates folding, ligand binding, and allosteric motions based on the energy landscape theory, we studied interplay among the three factors, in detail, for calmodulin domains. The analysis includes three conformational states and three binding states, resulting into nine states in total. We found multiple routes and their intriguing modulation by ligand concentration.