Solvent effect on the folding dynamics and structure of E6-associated protein characterized from ab initio protein folding simulations

Abstract

Solvent effect on protein conformation and folding mechanism of E6-associated protein (E6ap) peptide are investigated using a recently developed charge update scheme termed as adaptive hydrogen bond-specific charge (AHBC). On the basis of the close agreement between the calculated helix contents from AHBC simulations and experimental results, we observed based on the presented simulations that the two ends of the peptide may simultaneously take part in the formation of the helical structure at the early stage of folding and finally merge to form a helix with lowest backbone RMSD of about 0.9 Å in 40% 2,2,2-trifluoroethanol solution. However, in pure water, the folding may start at the center of the peptide sequence instead of at the two opposite ends. The analysis of the free energy landscape indicates that the solvent may determine the folding clusters of E6ap, which subsequently leads to the different final folded structure. The current study demonstrates new insight to the role of solvent in the determination of protein structure and folding dynamics.

Ab initio folding of extended α‐helix: A theoretical study about the role of electrostatic polarization in the folding of helical structures

“…In a previous study conducted by Zhang and coworkers, AHBC has successfully maneuvered the folding of a 17‐residue helical protein with best backbone root mean square deviation (rmsd) with respect to NMR structure of 0.5 Å . Further studies applying AHBC to the folding study of polyalanine mutants and the study of solvent effect on the folding dynamics of E6aP had also portrayed favorable results comparable to that of experiment . Therefore, in this work, we attempt to fold three proteins which comprise of exclusively α‐helical structures namely b30‐82 domain of F 1 F 0 adenosine triphosphate synthase from Escherichia Coli (E.coli) (2khk, PDB id: 2KHK) and N36 (N36, PDB id: 1AIK:N) and C34 (C34, PDB id: 1AIK:C) domain of gp41 from HIV‐1 envelope glycoprotein using AHBC scheme .…”

Adsorption and folding dynamics of MPER of HIV‐1 gp41 in the presence of dpc micelle

“…This self‐consistent procedure will be applied until convergence is reached. The scheme together with on‐the‐fly charge fitting in other studies has met some success in showing secondary structure stability,37, 38 protein folding,39–42 and modeling protein–ligand binding43, 44 more accurately compared to standard FF.…”

“…Following the result from earlier part where PPC scheme preserves helical structure of MPER better than AMBER03, MD production is done with PPC calculation of atomic charges of hydrogen bond donors and acceptors updated and refitted on the fly during the course of the simulation to reduce computational expense. This scheme, termed adaptive hydrogen bond charge (AHBC) scheme,42 has been successfully applied to study the effects of sequence mutation and the influence of environment on protein folding 39, 40…”

Conformational Response to Solvent Interaction and Temperature of a Protein (Histone h3.1) by a Multi-Grained Monte Carlo Simulation

“…Using the mode analysis they found that ‘solvent effects are important for the slowest motions but negligible for faster motion’ in low and high frequency modes, respectively. Xu et al [5], have performed MD simulation on a protein, E6ap, in water and trifluoroethanol with adaptive hydrogen bond-specific charge. From the analysis of the free energy, they found that ‘the solvent may determine the folding clusters of E6ap, which subsequently leads to the different final folded structure’.…”