Structural characterization of codon 129 polymorphism in prion peptide segments (PrP127-132) using the Markov State Models.

The human prion protein gene (PRNP) consists of two common alleles that encode either methionine or valine residues at codon 129. Polymorphism at codon 129 of the prion protein (PRNP) gene is closely associated with genetic variations and susceptibility to specific variants of prion diseases. The presence of these different alleles, known as the PRNP codon 129 polymorphism, plays a significant role in disease susceptibility and progression.

Graph-based analysis of H-bond networks and unsupervised learning reveal conformational coupling in prion peptide segments.

In this study, we employed a comprehensive computational approach to investigate the physical chemistry of the water networks surrounding hydrated peptide segments, as derived from molecular dynamics simulations. Our analysis uncovers a complex interplay of direct and water-mediated hydrogen bonds that intricately weave through the peptides. We demonstrate that these hydrogen bond networks encode critical information about the peptides' conformational behavior, with the dimensionality of these networks showing sensitivity to the peptides' conformations.