Temperature Accelerated Sliced Sampling (TASS)

Introduction

In this tutorial we will learn to use the strength of umbrella sampling (US) and metadynamics (MTD) together with temperature accelerated molecular dynamics/driven-adiabatic free energy dynamics (TAMD/d-AFED) for efficient sampling of high dimensional free energy landscape. Within this approach, the collective variables along which free energy surface is broad and unbound is sampled using US, the CV along which significantly high barriers are present is sampled using MTD and all the orthogonal CVs are sampled using TAMD/d-AFED. This tutorial follows the method used in the paper Shalini Awasthi and Nisanth N. Nair. "Exploring high dimensional free energy landscapes: Temperature accelerated sliced sampling". J. Chem. Phys. 146, 094108 (2017). It is recommended to read this paper for the details of parameters used for the simulation.

The basic form of Hamiltonian used in this method is:

In this tutorial we will explore the free energy surface of alanine tripeptide in vacuo as a function of four backbone dihedral angles (Φ1, Ψ1, Φ2, Ψ2) using TASS. Here, we are assuming that users are familiar with AMBER and can run MD simulation using PLUMED-AMBER interface. The first thing we need to do is build an initial structure using ff14SB force-field and relax this at 300K so that we can use this as the input for umbrella equilibration.  What we do is:

• Minimize (2000 steps)

• Heat (optional for small system)

• Relax (300K, 100ps)

This tutorial consist of three sections:

• Section 1: Umbrella Equilibration

• Section 2: TASS

• Section 3: Reweighting