Molecular insights into the mechanisms of cation-type specific stability and denaturation of poly-l-glutamate: a simulation study

Cation-induced conformational changes of peptide as a guide to developing insights into human diseases-related proteins have received a lot of attention. The interactions between poly-l-glutamate (PGA) and different cations, including Na⁺, K⁺ and Mg²⁺, respectively, are studied in solvent at a concentration of 1 M, and the behaviours of peptide with different cations are investigated. For Na⁺, an oscillatory stabilising process to α-helix PGA is found, in accordance with the uniform free-energy landscape, whereas for K⁺, an extended α-helix structure is formed by the terminal turns, suggesting a weaker attraction to charged head groups. For Mg²⁺, the bridged charged side chains are responsible for the maximum probability of helix state. These distinct structural changes can be attributed to the different interactions between charged head groups and cations. Both Na⁺ and K⁺ are mainly attracted around head groups by direct ion binding while Mg²⁺ is centrally trapped among adjacent charged head groups. In addition, a surprising shift of the backbone hydrogen bond, from intact state to intermediate state, is observed. This is opposite to the stabilising effect of Na⁺ around negatively charged head groups.