How side chains are modeled

Amino acid side chains tend to assume one of a discrete number of "rotamer" conformations. The rotamers used in CLC Genomics Workbench have been calculated from a non-redundant set of high-resolution crystal structures.

Side chains are modeled using a heat bath Monte Carlo simulated annealing algorithm, similar to the OPUS-Rota method [Lu et al., 2008]. The algorithm consists of approximately 100 cycles of simulation. In a single cycle, rotamers are selected for each side chain with a probability according to their energy. As the simulation proceeds, the selection increasingly favors the rotamers with the lowest energy, and the algorithm converges.

A local minimization of the modeled side chains is then carried out, to reduce unfavorable interactions with the surroundings.

Calculating the energy of a side chain rotamer

The total energy is composed of several terms:

Note: The atom interaction potential considers interactions within the modeled protein chain as well as with all other molecules in the downloaded PDB file (except water).

Local minimization of side chain

After applying a side chain rotamer from the library to the backbone, a local minimization may be carried out for rotations around single bonds in the side chain.

The potential to minimize with respect to bond rotation is composed of the following terms: