Calmodulin (CaM) is a complex signaling protein that transduces transient calcium ion signals. CaM's binding of calcium ions cause conformational changes, which interact with downstream proteins. Current research indicates that selective protein binding occurs through the mechanism of mutually induced conformational fit, which would explain how calcium dynamics in CaM would modulate its interaction.
Current research on CaM signaling and CaM–BT interaction includes experimental kinetic rate observations and coarse grain/all atom molecular dynamics simulations. Because protein signaling and protein–protein interaction is a new field of research, many observed interactions cannot be explained through experiment alone. The unification between simulation and experimental results is necessary to expand the predictive power of the theoretical approach and create general laws that explain the mechanics of signaling/protein–protein interactions.
The computational approach for modeling macro molecules is very resource intensive. The Hamiltonian equation in molecular dynamic software relates each atom to all other atoms in the system through kinetic, electrostatic, van der Waals, dihedra, bond, etc. energies. For example, the RRK polypeptide (CaMKII residues: 293-313) contains 21 residues and 318 atoms. For a single time step, the molecular dynamics software must perform energy calculations between every atom in the polypeptide, which is ~100,000 calculations. Since the time step must be in the sub picosecond range (to insure stability), several million time steps must be performed to obtain meaningful data. To remedy the large number of calculations involved in all atom simulations, the coarse grain simulation technique can be used. Current work from the biophysics group at the University of Houston uses open source coarse grain and all atomic models of CaM and wildtype/mutated binding targets of CaMKII in their research.