Dimensionality Reduction-Based Analysis of the Molecular Dynamics of G Protein-Coupled Receptors

G-protein coupled receptors (GPCRs) are the most abundant and varied family of transmembrane proteins in eukaryotic cells. Beyond their basic biological functions, they are relevant to pharmacology, as they are involved in a variety of human pathologies. Molecular dynamics (MD) are a reliable and effective simulation technique that allows us to investigate and examine the structure and activity that shape biomolecular signals. In this study, Dimensionality Reduction (DR) methods are applied to GPCR 3D simulations from a publicly accessible GPCR MD database to find the most effective simplified representation of these proteins that will help us to analyze their deactivation and activation pathways. The protein representations generated by several DR methods for inactive, intermediate, and active conformational GPCR states are compared through their entropy quantification and visual representation. In addition, experiments involve three types of MD data transformations, based on the 3D position of amino acids, the distances between the helices of the molecules, and the dihedral angles representing the torsion angles Psi and Phi of each amino acid. The results of our study show how some of the DR methods under investigation capture the smooth temporal evolution of the GPCR representations and their state transitions.