Anchoring of a hydrophobic heptapeptide (AFILPTG) on silica facilitates peptide unfolding at the abiotic-biotic interface.

Victor V Volkov ,Carole C Perry,Hendrik Heinz

doi:10.1039/d1cp02072b

Abstract

A hydrophobic heptapeptide, with sequence AFILPTG, as part of a phage capsid protein binds effectively to silica particles carrying negative charge. Here, we explore the silica binding activity of the sequence as a short polypeptide with polar N and C terminals. To describe the structural changes that occur on binding, we fit experimental infrared, Raman and circular dichroism data for a number of structures simulated in the full configuration space of the hepta-peptide using replica exchange molecular dynamics. Quantum chemistry was used to compute normal modes of infrared and Raman spectra and establish a relationship to structures from MD data. To interpret the circular dichroism data, instead of empirical factoring of optical activity into helical/sheet/random components, we exploit natural transition orbital theory and specify the contributions of backbone amide units, side chain functional groups, water, sodium ions and silica to the observed transitions. Computed optical responses suggest a less folded backbone and importance of the N-terminal when close to silica. We further discuss the thermodynamics of the interplay of charged and hydrophobic moieties of the polypeptide on association with the silica surface. The outcomes of this study may assist in the engineering of novel artificial bio-silica heterostructures.

Highlights

Short polypeptides offer an extensive playground for structural variability and functionalization, both of which are important for contemporary pharmacology and micro-engineering.[1,2] There is much interest in polypeptides that have the capacity to associate with mineral components: beside possible practical benefits, bio-mineral structural organization is a wide-ranging curiosity
Following the structural extraction protocol as described in the Material and Methods, in Fig. 1AA–CC we present theoretical fits of the observed spectral responses using Infrared, Raman and circular dichroism (CD) dispersions computed for 13 representative structural cases in water and 7 representative structural cases next to silica: see Electronic supplementary information (ESI).† In Fig. 3 and 4 we present the spectral sets of the structural cases which are used to fit the experimental data
We develop an approach in which we simulate structural variances with replica exchange and molecular dynamics, use density functional theory (DFT) to compute optical responses of anticipated structural cases, and evaluate probabilities of the structures to reproduce infrared, Raman and circular dichroism dispersions as observed experimentally

Summary

Introduction

Short polypeptides (less than 30 amino acids) offer an extensive playground for structural variability and functionalization, both of which are important for contemporary pharmacology and micro-engineering.[1,2] There is much interest in polypeptides that have the capacity to associate with mineral components: beside possible practical benefits, bio-mineral structural organization is a wide-ranging curiosity. Prediction of structure in relatively short polypeptides in configuration spaces of increasing order is a challenge. In recent years, assisted with artificial intelligence, prediction of structure has progressed from Q3 {helix, strand, coil}13,14 to Q8 {310 helix, a-helix, p-helix, b-strand, bridge, turn, bend, others} space.[15,16] For artificial intelligence is currently not able to explain neither the electric nor entropic aspects of interactions in bio-mineral composites. We cannot expect diffraction techniques, as well as, for example, NMR to be effective in providing detailed structural

Results

Discussion

Conclusion