Santanu Roy

Solvent and conformation dependence of amide I vibrations in peptides and proteins containing proline

We present a mixed quantum-classical model for studying the amide I vibrational dynamics (predominantly CO stretching) in peptides and proteins containing proline. There are existing models developed for determining frequencies of and couplings between the secondary amide units. However, these are not applicable to proline because this amino acid has a tertiary amide unit. Therefore, a new parametrization is required for infrared-spectroscopic studies of proteins that contain proline, such as collagen, the most abundant protein in humans and animals. Here, we construct the electrostatic and dihedral maps accounting for solvent and conformation effects on frequency and coupling for the proline unit. We examine the quality and the applicability of these maps by carrying out spectral simulations of a number of peptides with proline in D(2)O and compare with experimental observations.

Identifying Residual Structure in Intrinsically Disordered Systems: A 2D IR Spectroscopic Study of the GVGXPGVG Peptide

The peptide amide-I vibration of a proline turn encodes information on the turn structure. In this study, FTIR, two-dimensional IR spectroscopy and molecular dynamics simulations were employed to characterize the varying turn conformations that exist in the GVGX(L)PGVG family of disordered peptides. This analysis revealed that changing the size of the side chain at the X amino acid site from Gly to Ala to Val substantially alters the conformation of the peptide. To quantify this effect, proline peak shifts and intensity changes were compared to a structure-based spectroscopic model. These simulated spectra were used to assign the population of type-II β turns, bulged turns, and irregular β turns for each peptide. Of particular interest was the Val variant commonly found in the protein elastin, which contained a 25% population of irregular β turns containing two peptide hydrogen bonds to the proline C═O.

Analysis of 2D CS Spectra for Systems with Non-Gaussian Dynamics

We investigate how accurate different methods of the spectral line shape analysis work in two-dimensional correlation spectroscopy (2D CS) for systems with non-gaussian dynamics. A direct link is established between the frequency dependent correlation functions and a number of line shape metrics. Two model systems are constructed mimicking a typical molecular system with conventional gaussian and non-gaussian spectral dynamics. The frequency dependent correlation function and several line shape parameters extracted from the 2D CS spectra at different waiting times reveal dissimilar dynamics in different frequency domains in the non-gaussian case and similar dynamics in all domains in the gaussian case. The extracted frequency dependent correlation times agree well with the local dynamics in the underlying model for all analysis methods. We also find an extension of the existing line shape analysis methods that allows the extraction of the third-order correlation function.

Structural classification of the amide I sites of a beta-hairpin with isotope label 2DIR spectroscopy

We present a theoretical study of the possibility to use isotope label two-dimensional infrared (2DIR) spectroscopy to obtain site specific structural information in trpzip2. This small beta-hairpin peptide was designed as a model system for studying protein folding in beta-sheet structures. In order to unravel the folding mechanism, the surroundings of local sites should be characterized, which in principle is possible by using 2DIR in combination with isotope labeling. This requires a classification that correlates local structures to two-dimensional spectra. To this end, we provide the first spectral simulation of the isotope label spectra of all the amide I sites in trpzip2. We find that the anti-diagonal width of the 2DIR peak associated with a labelled site is a good measure of solvent exposure and the key parameter to distinguish between solvent exposed and internal sites. The diagonal widths are not particularly sensitive to this, but they do reveal the presence of slowly interconverting turn structures.

Theoretical Sum Frequency Generation Spectroscopy of Peptides

Vibrational sum frequency generation (SFG) has become a very promising technique for the study of proteins at interfaces, and it has been applied to important systems such as anti-microbial peptides, ion channel proteins, and human islet amyloid polypeptide. Moreover, so-called “chiral” SFG techniques, which rely on polarization combinations that generate strong signals primarily for chiral molecules, have proven to be particularly discriminatory of protein secondary structure. In this work, we present a theoretical strategy for calculating protein amide I SFG spectra by combining line-shape theory with molecular dynamics simulations. We then apply this method to three model peptides, demonstrating the existence of a significant chiral SFG signal for peptides with chiral centers, and providing a framework for interpreting the results on the basis of the dependence of the SFG signal on the peptide orientation. We also examine the importance of dynamical and coupling effects. Finally, we suggest a simple method for determining a chromophore’s orientation relative to the surface using ratios of experimental heterodyne-detected signals with different polarizations, and test this method using theoretical spectra.

Computer simulation of methanol exchange dynamics around cations and anions

In this paper, we present the first computer simulation of methanol exchange dynamics between the first and second solvation shells around different cations and anions. After water, methanol is the most frequently used solvent for ions. Methanol has different structural and dynamical properties than water, so its ion solvation process is different. To this end, we performed molecular dynamics simulations using polarizable potential models to describe methanol-methanol and ion-methanol interactions. In particular, we computed methanol exchange rates by employing the transition state theory, the Impey-Madden-McDonald method, the reactive flux approach, and the Grote-Hynes theory. We observed that methanol exchange occurs at a nanosecond time scale for Na(+) and at a picosecond time scale for Cs(+), Cl(-), and I(-). We also observed a trend in which, for like charges, the exchange rate is slower for smaller ions because they are more strongly bound to methanol.

Marcus Theory of Ion-Pairing

We present a theory for ion pair dissociation and association, motivated by the concepts of Marcus theory of electron transfer. Despite the extensive research on ion-pairing in many chemical and biological processes, much can be learned from the exploration of collective reaction coordinates. To this end, we explore two reaction coordinates, ion pair distance and coordination number. The study of the correlation between these reaction coordinates provides a new insight into the mechanism and kinetics of ion pair dissociation and association in water. The potential of mean force on these 2D surfaces computed from molecular dynamics simulations of different monovalent ion pairs reveal a Marcus-like mechanism for ion-pairing: Water molecules rearrange forming an activated coordination state prior to ion pair dissociation or association, followed by relaxation of the coordination state due to further water rearrangement. Like Marcus theory, we find the existence of an inverted region where the transition rates are slower with increasing exergonicity. This study provides a new perspective for the future investigations of ion-pairing and transport.