To run an MD simulations using Amber force field ff14SB:
- Convert your protein to an ICM object.
- MolMechanics/Run MD Simulation
- Use the drop down box to select the protein.
- Select whether or not you wish to solvate the protein.
- Select the length of time for the simulation in ns.
- A custom box can be used but in MD the box must cover the entire object, with some margin. Box is used to create periodic system, where everything repeats in adjacent boxes. In general, there is rarely a good reason to not use automatic default. If one does use custom box, it is to make it bigger, not smaller.
- Click OK.
Restraints There are different ways to apply restraints during MD:
- Positional Restraints (Tethering to Original Positions) This method tethers distal regions of the protein or system to their original coordinates. It is useful when you want those parts to remain relatively static in absolute space—for example, anchoring terminal residues or regions far from the ligand. This is the option in the GUI or you can use the option -rl in runMDopenMM script
- Internal Restraints ( Ca=Ca Distance Restraints) This method restrains internal geometry-such as keeping the distance between alpha carbons (Ca) of key residues. It allows the system to move globally but helps preserve the relative structure of specific elements (e.g., loops or helices).
The conformation snapshots are stored at regular time intervals during the MD simulation and are embedded in the ICM object as a stack.
Results Analysis:
Right click on the stack of MD snapshots in the ICM workspace and choose Stack Calculations. In this dialog box you can analyze
- Distance - Select a pair of atoms or use green and orange selections for closest distance. A table and plots of the distance will be displayed.
- RMSD to Reference - Read in a separate object as a reference and make the selection you want to analyze. You can choose to analyze the structures 'static' or superimpose. A table and plot of the RMSDs are displayed. This is a useful tool for analysis of a Molecular Dynamics run. Your x-axis will be the time in ns / number of conformations so if you chose 1ns and 50 conformations (snapshots) then each point is 1ns/50 = 0.02 ns
- RMSF - Root mean square fluctuation indicates positional differences in structure during a simulation. There is a Static and Superimpose option - the superimpose option follows protocol described here. You can provide two selections: for superposition using orange selection and regular "green" selection for RMSF calculation. By default it (if no selections are provided) backbone from all residues will be used.
- Ligand Contacts - This method uses our Interaction Lists macro from our docking hitlist. Select the ligand and then the macro will be called for each MD snapshot in the stack and calculates number of: hydrophobic(apol), hydrogen bond don/acc (hba/hbd) and positive/negative. Individual residues can be included if you check this opti
- Torsion - Select a pair of atoms on a rotatable bond to calculate the torsion angle.
- Area - use green and orange selections to calculate differences in area
- RTCNN - use green and orange selections for receptor/ligand respectively to calculate RTCNN docking score.
- ClusterTree - make a selection of atoms to compare and then a cluster tree will be displayed. You can then 'select-tree{select} a diverse set of conformations in the tree.