Molecular interaction of di-ester bonded cationic Gemini surfactants with pepsin: in vitro and in silico perspectives

Abstract

The implications of surfactant-enzyme/protein interactions in a variety of fields, including biotechnology, cosmetics, paints and pharmaceuticals, have attracted a lot of attention in contemporary studies. Herein, we have employed several in vitro and in silico techniques such as excitation and absorption spectroscopies, circular dichroism and FT-IR spectroscopies, density functional and molecular dynamics simulations to understand the interaction behavior of oxy-diester-based green cationic Gemini surfactants, N¹,N¹,N¹⁴,N¹⁴-tetramethyl-2,13-dioxo-N¹,N¹⁴-dialkyl-3,6,12-tetraoxateradecane-1,14-diaminiumdichloride (abbreviated as C_m-E2O2-C_m, where 'm' stands for alkyl chain length, m = 12 and 14) with one of the main digestive proteins, pepsin. The spectroscopic techniques confirm the static quenching effect of surfactants on pepsin. The calculated physical parameters (K_sv, K_b and ΔG) and their order reveal the distinguished implications for the surfactants' chain lengths. The spontaneity of interaction was also confirmed by negative Gibbs free energy change values. The extrinsic spectroscopic study with pyrene as fluorescence probe, FT-IR and CD techniques indicated a potential conformational change in pepsin induced by the Gemini surfactants. DFT, docking and MD simulations provided the theoretical understanding regarding the quantum mechanical environment, location of binding and stability of the protein-surfactant complexation in energy terms. We believe this study will be a humble addition to our existing knowledge in the field of protein-surfactant interactions.Communicated by Ramaswamy H. Sarma.

Keywords: Cm-E2O2-Cm Gemini surfactants; DFT; MD simulation; binding; docking; pepsin; spectroscopy.