Computational Systems Biochemistry Group

Crystallography provides impressive images of biological macromolecules with atomic resolution, yet they are static pictures. Thinking of the function of these molecules, dynamic features like conformational variation, ligand binding, protein folding come to mind. Our dynamic picture relies on spectroscopical observations that contain little or no information about the molecular geometry. At present we have no technique that provides high resolution in time and space at the same time. It would be desireable to watch the molecule at atomic resolution while it performs its function.

One way to address this problem and to study the dynamic behaviour is computer simulation of molecular dynamics (MD) which solves Newton's equations of motion

$\begin{equation} F_i=m_i a_i, \end{equation}$

F_i is the force, m_i the mass, and a_i the acceleration of atom i, for a system of N atoms interacting according to a potential energy. The force can be calculated from the negative gradient of the potential V

$\begin{equation} F_i=-\frac{\partial V}{\partial r_i}=m_i \frac{\partial^2 r_i}{\partial t^2}. \end{equation}$

Thus the equation relates the derivative of the potential energy to the changes in position as a function of time. Once the initial coordinates and velocities of all atoms of our system are known and we are in possesion of a model of the potential energy surface, Newton's equations of motion can be integrated to compute the atom positions and velocities in the future. These trajectories provide insight into the systems conformational flexibility as the system explores different accessible parts of the phase space.

As we have absolute control over a computer simulation it is an intriguing idea to carry out experiments like docking of two protein subunits, ligand binding or mutations.

Paratool

Easy generation of force field parameters

Paratool is a plugin for the popular molecular visialization program VMD and provides a graphical interface for force field parametrizations of molecules that are not contained in your force field. It is designed to generate CHARMM or AMBER compliant parameters (while it is more specialized on CHARMM).

The plugin helps you to generate the molecule or the moleular fragment that should be parametrized and to set up the necessary quantumchemical calculations (you'll need Gaussian, later versions will also support GAMESS). Paratool reads the logfiles of the QM simulations, computes force field parameters for bonds, angles dihedrals and impropers by transforming the Hessian into internal coordinates and converting all values into units based on kcal/mol, Å and degrees. You can assign atom types and the corresponding VDW parameters from a list of already existing types or generates new types (all chemical elements H - Rn supported). The charges can be determined using restricted electrostatic potential fitting RESP (AMBER style) or CHARMM style charges using their supramolecular approach which requires another Gaussian calculation.

Paratool generates input for all necessary external programs collects and compiles all the necessary data, organizes and displays them neatly in lists and projects them onto your molecule in VMD. Finally it will write the topology and parameter files you'll need to build the molecule using psfgen and run your simulation in your favourite simulation package, e.g. NAMD.

Download

Paratool is part of the version 1.8.6 of VMD, which you can download here.

Documentation

Even though Paratool simplifies force field parametrization a lot you'll still need to know what you are doing. We are currently preparing a manuscript that will give a detailed overview over the complete force field parametrization process. Please check back!

Paratool's user guide is a practical guide through the parametrization procedure but also also contains a reasonable amount of background information.

Author

Dr. Jan Saam with contributions from Peter Freedolino and John Eargle.

		Molecular Dynamics Simulations
Home Research VirtualLiver People Publications Software Positions Events Contact		Crystallography provides impressive images of biological macromolecules with atomic resolution, yet they are static pictures. Thinking of the function of these molecules, dynamic features like conformational variation, ligand binding, protein folding come to mind. Our dynamic picture relies on spectroscopical observations that contain little or no information about the molecular geometry. At present we have no technique that provides high resolution in time and space at the same time. It would be desireable to watch the molecule at atomic resolution while it performs its function. One way to address this problem and to study the dynamic behaviour is computer simulation of molecular dynamics (MD) which solves Newton's equations of motion $\begin{equation} F_i=m_i a_i, \end{equation}$ F_i is the force, m_i the mass, and a_i the acceleration of atom i, for a system of N atoms interacting according to a potential energy. The force can be calculated from the negative gradient of the potential V $\begin{equation} F_i=-\frac{\partial V}{\partial r_i}=m_i \frac{\partial^2 r_i}{\partial t^2}. \end{equation}$ Thus the equation relates the derivative of the potential energy to the changes in position as a function of time. Once the initial coordinates and velocities of all atoms of our system are known and we are in possesion of a model of the potential energy surface, Newton's equations of motion can be integrated to compute the atom positions and velocities in the future. These trajectories provide insight into the systems conformational flexibility as the system explores different accessible parts of the phase space. As we have absolute control over a computer simulation it is an intriguing idea to carry out experiments like docking of two protein subunits, ligand binding or mutations. Paratool Easy generation of force field parameters Paratool is a plugin for the popular molecular visialization program VMD and provides a graphical interface for force field parametrizations of molecules that are not contained in your force field. It is designed to generate CHARMM or AMBER compliant parameters (while it is more specialized on CHARMM). The plugin helps you to generate the molecule or the moleular fragment that should be parametrized and to set up the necessary quantumchemical calculations (you'll need Gaussian, later versions will also support GAMESS). Paratool reads the logfiles of the QM simulations, computes force field parameters for bonds, angles dihedrals and impropers by transforming the Hessian into internal coordinates and converting all values into units based on kcal/mol, Å and degrees. You can assign atom types and the corresponding VDW parameters from a list of already existing types or generates new types (all chemical elements H - Rn supported). The charges can be determined using restricted electrostatic potential fitting RESP (AMBER style) or CHARMM style charges using their supramolecular approach which requires another Gaussian calculation. Paratool generates input for all necessary external programs collects and compiles all the necessary data, organizes and displays them neatly in lists and projects them onto your molecule in VMD. Finally it will write the topology and parameter files you'll need to build the molecule using psfgen and run your simulation in your favourite simulation package, e.g. NAMD. Download Paratool is part of the version 1.8.6 of VMD, which you can download here. Documentation Even though Paratool simplifies force field parametrization a lot you'll still need to know what you are doing. We are currently preparing a manuscript that will give a detailed overview over the complete force field parametrization process. Please check back! Paratool's user guide is a practical guide through the parametrization procedure but also also contains a reasonable amount of background information. Author Dr. Jan Saam with contributions from Peter Freedolino and John Eargle.