Effects of surface hydrophobicity on the conformational changes of polypeptides of different length

Abstract

We studied the effects of surface hydrophobicity on the conformational changes of different length polypeptides by calculating the free energy difference between peptide structures using the bias-potential Monte Carlo technique and the probability ratio method. It was found that the hydrophobic surface plays an important role in the stability of secondary structures of the polypeptides with hydrophobic side chains. For short GAAAAG peptides, the hydrophobic surface destabilizes the α helix but stabilizes the β hairpin in the entire temperature region considered in our study. Interestingly, when the surface hydrophobic strength ε(hpsf)≥ε(hp), the most stable structure in the low temperature region changes from α helix to β hairpin, and the corresponding phase transition temperature increases slightly. For longer GAAAAAAAAAAG peptides, the effects of the relatively weak hydrophobic surface (ε(hpsf) < ε(hp)) on α-helical structures may be neglected, while the relatively strongly hydrophobic surface (ε(hpsf)≥ε(hp)) leads to the obvious partial helicity loss. In contrast, the stability of β structures can be enhanced significantly by the hydrophobic surface, especially by the strongly hydrophobic surface, at low and intermediate temperatures. At high temperatures, in addition to thermal fluctuations, the strongly hydrophobic surface (ε(hpsf)>ε(hp)) may further disturb the formation of both α-helical and β structures. Moreover, the phase transition temperature between α-helical structures and random coils significantly decreases due to the helicity loss when ε(hpsf)>ε(hp). Our findings provide a basic and quantitative picture for understanding the effects of a hydrophobic surface on the conformational changes of the polypeptides with hydrophobic side chains. From an application viewpoint, the present study is helpful in developing alternative strategies of producing high-quality biological fibrillar materials and functional nanoscale devices by the self-assembly of the polypeptides on hydrophobic surfaces.

Characterizing the Switching Transitions of an Adsorbed Peptide by Mapping the Potential Energy Surface

“…This preference in the gas phase for short polyalanines is not inconsistent with earlier results of others. , It is also in line with the work of Park and Goddard, who showed that polyalanine α-helixes are stabilized by dipole–dipole interaction energy that increases with the number of residues. This result is corroborated by other studies that show α-helical global minima for long polyalanines. − More recently, studies of polyalanine and polyalanine derivatives adsorbing on solid surfaces have indicated the formation of α-helixes through simulation (via a course-grained Monte Carlo study) and both α-helixes , and 3 10 -helixes through experiment (via synthesis of self-assembled monolayers), although it must be noted that none of these studies precisely replicate the system studied here. The second difference between the results obtained here and those of Mijajlovic and Biggs is the absolute values of the switching energies: they are significantly higher and lower for 3 10 → 2 7 and α → 3 10 switches, respectively.…”

Promoting endothelial cell affinity and antithrombogenicity of polytetrafluoroethylene (PTFE) by mussel-inspired modification and RGD/heparin grafting

“…This should facilitate protein adhesion, and, more importantly, RGD itself can interact with the receptors on the cell membrane to enhance cell adhesion, thus resulting in further enhanced cell adhesion. 51, 52 It was found that the difference of cell attachment on RGD-PTFE and R/H-PTFE was not statistically significant, indicating that the addition of heparin did not further improve cell attachment. Thus, RGD may have played the major role in facilitating cell attachment.…”

Length-dependent β-sheet growth mechanisms of polyalanine peptides in water and on hydrophobic surfaces

“…Computer simulation provides a powerful tool of studying adsorption and aggregation of polypeptides onto various substrate surfaces at the atomic level. However, due to the complicated nature of molecular interactions and long time scale involved, the majority of simulation studies merely focused on adsorption behavior and conformational transition of a single polypeptide on surfaces and membranes [15][16][17][18][19][20][21][22]. Only a few simulation studies focused on the influences of surface characteristics on peptide aggregations [23][24][25].…”

“…Due to the simplicity and hydrophobicity of its side chains, poly(A) has been a popular model peptide in both computational [22,[26][27][28][29][30] and experimental [31][32][33][34][35][36] studies on peptide aggregation. Very recently, Bernacki and Murphy synthesized poly(A) peptides with different chain lengths (A7 to A25) and investigated the length-dependent aggregation properties of uninterrupted poly(A) peptides in aqueous solutions [36].…”