Steered Molecular dynamics simulations

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 Steered molecular dynamics (SMD) simulation is a type of molecular dynamics simulation that is used to study the response of a biomolecule to an applied force or an external perturbation.

In SMD simulations, a force is applied to a subset of atoms within the biomolecule, typically using an external potential, to simulate the effect of a physical process such as protein unfolding, ligand binding or transport of ions across a membrane. The force is applied in a controlled and gradual manner, allowing the biomolecule to respond to the force and explore different conformational states.

During an SMD simulation, the forces acting on the subset of atoms are continuously updated to maintain a specific pulling speed or force constant. The resulting changes in the structure and dynamics of the biomolecule can be analyzed to provide insights into its function and behavior under different conditions.

SMD simulations can be used to study a wide range of biological processes, such as protein-ligand interactions, protein-protein interactions, and membrane transport. They can also be combined with other computational techniques, such as free energy calculations, to provide a more detailed understanding of the thermodynamics and kinetics of the process being studied.

Overall, SMD simulations provide a powerful tool for studying the response of biomolecules to external forces or perturbations and have applications in a variety of fields, including drug discovery, materials science, and biophysics.

In steered molecular dynamics (SMD) simulations, the Jarzynski average and potential mean force are two important quantities that can be used to analyze the response of a biomolecule to an applied force or an external perturbation.


The Jarzynski average, is a quantity that expresses the free energy difference between two equilibrium states of a system and can be calculated from nonequilibrium simulations. In SMD simulations, the Jarzynski average can be used to estimate the binding free energy of a ligand to a protein or the stability of a protein structure under mechanical stress. Jarzynski's equality is a fundamental result in statistical mechanics that provides a way to calculate the free energy difference between two equilibrium states of a system from nonequilibrium simulations. The Jarzynski average is a quantity that expresses this free energy difference and is calculated using the Jarzynski's equality.


The Jarzynski's equality states that the exponential average of the work done on the system during a nonequilibrium process is equal to the exponential of the negative free energy difference between the initial and final equilibrium states of the system. Mathematically, the equality is expressed as:


⟨exp(-βW)> = exp(-ΔF/ kT)


where ⟨exp(-βW)> represents the exponential average of the work done on the system, β is the inverse temperature, W is the work done on the system during the nonequilibrium process, ΔF is the free energy difference between the initial and final equilibrium states of the system, k is the Boltzmann constant, and T is the temperature.


The Jarzynski average is then calculated as:


ΔF = -kTln(⟨exp(-βW)>)


This equation allows researchers to calculate the free energy difference between two equilibrium states of a system using nonequilibrium simulations, which can be much faster and more efficient than traditional equilibrium simulations.


The potential mean force (PMF) is another important quantity in SMD simulations that describes the energy landscape of a system as a function of a reaction coordinate or a collective variable. The PMF can be calculated by integrating the force acting on the subset of atoms being pulled or pushed during the SMD simulation. The resulting PMF can provide insights into the thermodynamics and kinetics of the process being studied, such as the binding of a ligand to a protein or the unfolding of a protein under mechanical stress.


The work done during an SMD simulation is another important quantity that can be used to analyze the response of a biomolecule to an external force. The work is defined as the integral of the force acting on the subset of atoms being pulled or pushed, and can be used to calculate the work necessary to deform or manipulate a biomolecule, such as the work necessary to unfold a protein or to transport an ion across a membrane.



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