Daughter of Turnip

Daughter of Turnip (or DOT) is a molecular interaction algorithm and programme that does a rapid computation of the electrostatic potential energy between two proteins or other charged molecules.

DOT exhaustively tests all six degrees of freedom, rotational and translational, and produces a grid of approximate interaction energies and orientations. It is able to do this because the problem is cast as the convolution of the potential field of the first molecule and any rotated charge distribution of the second. The algorithm lends itself to both parallelization and vectorization, permitting huge increases in computational speed over other methods for obtaining the same information. DOT is expected to be particularly useful as a rapid screen to find configurations for more detailed study using exact energy models.

DOT is based on TURNIP, a programme developed by Victoria A. Roberts for the study of electrostatically interacting proteins.

Detection and analysis of the interactions of biological macromolecules is a key problem in molecular biology. Many complex cellular regulatory systems are controlled through such interactions. The subtle web of chemical processes that constitutes cellular metabolism depends on the interactions of macromolecules. Knowledge of the most stable relative orientations between interacting macromolecules is essential in understanding how proteins associate with one another. Knowledge of specific protein-to-protein interactions may be applied to protein subunit aggregation (for the study, e.g., of supramolecular structures), to computer-aided drug design, and to fundamental problems of cellular signaling and expression.

Most methods for modeling macromolecular interactions depend on energy minimization, molecular dynamics, free energy simulations, and related methods to find energy minima. DOT takes a different approach. The objective of DOT is to perform a rapid calculation that will immediately identify all of the "hot spots"--the relatively small number of configurations that are notably more favorable than others. The resulting list of possibilities can then be examined in greater detail by more comprehensive (and computationally expensive) methods.

DOT achieves its objective by efficiently enumerating all of the possibilities, thereby reducing the minimization problem to one of scanning the results. DOT exhaustively tests all six degrees of freedom, rotational and translational. The energies calculated by DOT include electrostatic interaction energies and van der Waals collisions, and DOT can also count the number of atoms that are in contact between the two molecules. The result of the calculation is a grid of approximate interaction energies and orientations. Since DOT is restricted to rigid molecules, calculates energies only on a regular grid in Cartesian space, and makes some approximations in the potential energy calculations, the favorable points found by DOT are not exact, but should be further analyzed by energy minimizations, molecular dynamics, or other related techniques. DOT does not currently take solvation energy into account, and thus it is most successful at present where the molecular interaction is known to be dominated by electrostatic forces. (Methods are presented in this paper that enable the calculation of buried surface area, which can be used to approximate solvation effects.) In most situations, however, DOT will quickly accomplish what have been among the most rate-limiting steps in the typical search of configuration space.

DOT (Daughter of Turnip) is based on TURNIP, a program developed by [Victoria A. Roberts] for the study of electrostatically interacting proteins. TURNIP did not scale well to larger problems, evaluated only a simple Coulombic electrostatic model, and did not consider geometric fit apart from constraining the closest distance between protein molecules. DOT addresses these issues. The electrostatic model used by DOT requires the calculation of a potential field once during the calculation, but only once: the use of full Poisson-Boltzmann models, therefore, does not significantly affect the cost of the computation. The method for detection of overlap between two molecules used by DOT can also count the number of atoms close to contact, giving a direct estimate of the buried surface area. (Ten Eyck, et al., 1995)

My involvement

The DOT algorithm was modified by me for use in my research at the Dr. Carlos J. Camacho Laboratory in the ClusPro and SmoothDock programmes.

References

Further reading

• Mandell JG, Roberts VA, Pique ME, Kotlovyi V, Mitchell JC, Nelson E, Tsigelny I, Ten Eyck LF (2001). Protein docking using continuum electrostatics and geometric fit. Protein Eng, 14:105–113.
• Geist GA, Beguelin A, Dongarra J, Jiang W, Manchek R, Sunderam VS (1994). PVM: Parallel Virtual Machine - A User's Guide and Tutorial for Networked Parallel Computing. MIT Press, Cambridge. (Additional information can be found at the PVM Home Page).

External links

• DOT official website (requires registration to download)
• Surveying Molecular Interactions with DOT