Atomistic Insights Into the Regulatory Mechanisms Mediated by Post- Translational Modifications: Molecular Dynamics Investigations

Abstract

Post-translational phosphorylation is a ubiquitous mechanism for cellular regulation, playing a crucial role in a diverse array of processes. At the molecular level, the phosphorylation seems to cause electrostatic perturbations which modulate the energy landscape governing protein folding, activity, protein-protein interactions and, conformational dynamics. However, details on structural effects induced by phosphorylation of proteins are still poorly understood. In this context, computational simulations recently provided a valuable alternative in the elucidation of principles and mechanisms of protein phosphorylation. In the present contribution, we review several recent studies devoted to molecular dynamics simulations of phospho-proteins with particular attention to proteins involved in the p53 pathway, ubiquitin pathway, protein kinases and intrinsically disordered proteins. Since application of biomolecular simulations to the investigation of mechanisms related to protein phospho-regulation is a newborn field for computational biology, our contribution could provide a suitable framework to plan future researches and to rationalize the available data in the field. Keywords: Molecular Dynamics Simulations, Phosphorylation, Conformational Change, Electrostatic Interaction, Kinase, p53, Ubiquitin, phosphorylation, loop-sheet-helix, Murine Double Minute clone 2