Molecular dynamics simulations represent a powerful tool to gain insights into structural and dynamical features of biomolecular systems. Nevertheless, their recognized limitation in terms of achievable timescales becomes particularly severe when dealing with slow processes. In such cases, the employment of enhanced sampling methods, which allow accelerating the characterization of rare events in a timeframe consistent with conventional computational resources, results as crucial. In particular, such advanced techniques have proven highly valuable in the context of protein folding and, specifically, to explore the conformational ensemble spanned by intrinsically disordered proteins (IDPs). Here, we describe how to set up molecular dynamics simulations with one of these enhanced sampling approaches (namely, Parallel Tempering Metadynamics in the Well-Tempered Ensemble) using the NTAIL peptide as a test case.
Keywords: Collective variables; Molecular dynamics; NTAIL; Replica Exchange; Well-Tempered Ensemble; Well-tempered metadynamics.