A Practical Guide to Kinetics Calculation of Protein Conformational Change using Frequency Adaptive Metadynamics

Abstract

The kinetic properties in biological systems are important for understanding biomolecular functions and are of great importance for drug discovery. However, how to precisely calculate the kinetics of rare events occurring in biomolecular systems with computational methods remains a big challenge. Recently, a variant of metadynamics, namely, frequency-adaptive metadynamics (FAMetaD), has been developed to calculate the unbiased transition time from biased molecular dynamics simulations with high efficiency. In this chapter, we provided a detailed tutorial about how to perform and analyze FAMetaD simulations by taking a simple pentapeptide as the model system which however has a complex free energy landscape with multiple conformational states. With the help of this tutorial, we hope that non-experienced users can master the skill of performing and analyzing FAMetaD simulations and apply to their own biological problems.