Reconstructing the infrared spectrum of a peptide from representative conformers of the full canonical ensemble

Abstract

Leucine enkephalin (LeuEnk), a biologically active endogenous opioid pentapeptide, has been under intense investigation because it is small enough to allow efficient use of sophisticated computational methods and large enough to provide insights into low-lying minima of its conformational space. Here, we reproduce and interpret experimental infrared (IR) spectra of this model peptide in gas phase using a combination of replica-exchange molecular dynamics simulations, machine learning, and ab initio calculations. In particular, we evaluate the possibility of averaging representative structural contributions to obtain an accurate computed spectrum that accounts for the corresponding canonical ensemble of the real experimental situation. Representative conformers are identified by partitioning the conformational phase space into subensembles of similar conformers. The IR contribution of each representative conformer is calculated from ab initio and weighted according to the population of each cluster. Convergence of the averaged IR signal is rationalized by merging contributions in a hierarchical clustering and the comparison to IR multiple photon dissociation experiments. The improvements achieved by decomposing clusters containing similar conformations into even smaller subensembles is strong evidence that a thorough assessment of the conformational landscape and the associated hydrogen bonding is a prerequisite for deciphering important fingerprints in experimental spectroscopic data.

Synthesis and Quantitative Analysis of Glycans Conjugated to Gold Nanoparticles

“…Since the N ‐glycan and gold nanoparticle each has its own characteristic FTIR signals, it is easy to tell the difference when the N ‐glycan is conjugated to the particle. The FTIR results showed that the hybrid‐type N ‐glycan is conjugated to the gold nanoparticles, as evidenced by the presence of representative signal peaks at specific FTIR wavelengths [26–30] . In addition, previous studies have indicated that monoclonal antibodies PG9 and PG16 exhibit strong binding to the hybrid‐type N ‐glycans G10 [2] .…”

Mapping the electronic transitions of protonation sites in peptides using soft X-ray action spectroscopy

“…The lowest REMD energy conformation of each identified cluster was chosen as the representative conformer of that cluster and considered for the calculation of the absorption spectra, as discussed by Kotobi and co-workers. 47 A Boltzmann weighting factor based on the REMD energy differences between the representative conformers and normalized by the cluster population was employed to estimate the statistical relevance of the various metastable states and to obtain weighted average spectra considering a canonical ensemble of the conformers. Conformers, from REMD, having a weighting factor less than 2% of the contribution were assumed to be negligible.…”

Gaining More Insights from Synchrotron-Based X-ray Spectroscopy for Alkali Ion Rechargeable Batteries

“…Beyond the battery community, the field of condensed matter and catalysis has witnessed the significant power of ML in X-ray spectroscopy. 115,116,121,122 For instance, the direct conversion of XANES data into the radial distribution function (RDF) was accomplished using an artificial neural network (ANN) ML model (Figure 7c). More recently, the incorporation of explainability into the graph neural network (GNN) architecture not only facilitates accurate predictions of XANES spectra but also enhances our current comprehension of XANES (Figure 7d).…”