Efficient Estimation of Binding Kinetics using Scaled Non-Bonded Interactions and Harmonic Restraints

Abstract

Understanding the thermodynamics and kinetics of protein-ligand interactions is crucial for computational drug discovery. In this project, we simulate a small host-guest system where the ligand is a single, uncharged Lennard-Jones (LJ) particle, and the binding site is an 11-particle icosahedral pocket made from the same atom type; the system is simulated in a (3.00859 nm)3 periodic box filled with 860 TIP3P waters. We first tuned the LJ parameter ε to construct a system that realistically mimics a protein-ligand binding system.