Editing ChargeCalculator:Motivation (section)

=Molecular Dynamics simulations=

''Molecular dynamics'' uses classical mechanics to model molecular systems. The energy of a molecular system is calculated using ''force fields''. Force fields express the energy of the molecular system as a sum of energy terms (e.g., for bonded and non-bonded interactions), each expressed as a function of certain parameters. Atomic charges are used in the estimation of the electrostatic contribution to the total energy of the molecular system.

In many force fields the parameters may have been fitted to work optimally with a certain kind of ''internal'' atomic charges (e.g., AMBER uses RESP charges, CHARMM uses CHARMM-like charges, etc.). Mixing ''external'' charges into such a force field may thus not give an optimal behavior of the force field. Unpredictable results may be obtained when employing charges which are fundamentally different from those originally involved in the development of the force field. Secondary structure elements might deviate from their optimal form (bent or partly unwound alpha helices). On the other hand, this is a very effective way to sample conformations of the molecule otherwise inaccessible to the simulation. You may then minimize each new conformation, and run separate classical simulations. This can be a great advantage when simulating processes that involve large conformational changes (e.g., signal transduction via membrane proteins).

Note that many widely used force fields consider a fixed charge model, meaning that atomic charges remain unchanged throughout the entire simulation. By nature, the empirical model used by '''ACC''' produces atomic charges which are specific to the 3D structure, and thus respond to changes in molecular conformation or chemical environment (e.g., movement of ions closer to the binding site). This means that if you plan to use a force field with a fixed charge model but you still want to allow the electrostatic environment to evolve during the simulation, you will have to update the atomic charges manually at certain intervals during the simulation (e.g., by running '''ACC''' on snapshots of the molecular structure, and then continuing the simulation with the updated charges). While such a procedure is easy to implement, always remember to proceed with care when mixing charges which are ''external'' to the force field, with the rest of the force field that has been developed together with a set of ''internal'' charges.

Many molecular dynamics simulation tools are available. Currently, '''ACC''' does not provide input files specific to each simulation package, mainly because there are too many of them, each different and continuously evolving. ACC does provides molecular structure files containing charges (mol2, pqr), as well as files containing only charges (.mchrg) which can be easily incorporated in other file formats. 

However, if you are primarily interested in running molecular dynamics, we recommend to look into [http://pubs.acs.org/doi/abs/10.1021/jp004368u ''ReaxFF''], a force field which works with atomic charges that respond to changes in conformation and chemical environment. The principles of atomic charge calculation in ''ReaxFF'' are similar to those applied by '''ACC'''. Efficient ReaxFF implementations can be found in [http://lammps.sandia.gov/doc/pair_reax.html LAMMPS] or the commercial tool [http://www.scm.com/ReaxFF/ SCM].

'''Start by having a look at the main [[ChargeCalculator:Terminology | terms]] used by ACC, or return to the [[ChargeCalculator:UserManual | Table of contents]].'''