Molecular Dynamics Computations for Proteins: A Case Study in Membrane Ion Permeation

摘要: Computer simulation can provide an atomic-level view of protein structure and function that is unattainable with experiments alone. In this chapter, we demonstrate how molecular dynamics (MD) reveal the microscopic mechanisms biomolecular activity. particular, illustrate quantitative value MD by exploring ion channel proteins allow selective permeation charged molecules across cell membranes to control our nervous systems chemical activity in body. We begin introducing basic statistical mechanical formulation methodological aspects modern day simulations. then discuss analyze a obtain mechanistic insight through calculation various properties. Special attention given thermodynamic calculations, which are driving forces function. explain calculate free energies equilibrium constants using potential mean force (PMF) energy perturbation (FEP) techniques as well use more advanced sampling approaches. These methods used study gramicidin A (gA) energetics arginine side chain translocation lipid bilayer assess models voltage-gated activation. Keywords: mechanical fields; MD methods; MD simulation; MD trajectories; MM fields