A CLP Approach to the Protein Side-Chain Placement Problem
Selecting conformations for side-chains is an important subtask in building three-dimensional protein models. Side-chain placement is a difficult problem because of the large search space that has to be explored. We show that the side-chain placement problem can be expressed as a CLP program in which rotamer conformations are used as values for finite domain variables, and bad atomic clashes involving rotamers are represented as constraints. We present a new side-chain placement method that uses a series of automatically generated CLP programs to represent successively tighter side-chain packing constraints. By using these programs iteratively our method produces side-chain conformation predictions whose accuracy is comparable with that of other methods. The resulting system provides a testbed for evaluating the quality of protein models obtained using different domain enumeration heuristics and side-chain rotamer libraries.
KeywordsMinimum Probability Rotamer Library Root Mean Square Distance Rotamer Conformation Combinatorial Search Space
Unable to display preview. Download preview PDF.
- 4.M. Carlsson, G. Ottosson, and B. Carlson. An open-ended finite domain constraint solver. Proc. Programming Languages: Implementations, Logics, and Programs, 1997.Google Scholar
- 16.H. Kono and J. Doi. A new method for side-chain conformation prediction using a hopfield network and reproduced rotamers. J. Comp. Chem., 17:1667–1683, 1996.Google Scholar
- 20.M. Levitt, M. Gerstein, E. Huang, S. Subbiah, and J. Tsai. Protein folding: The endgame. Annu. Rev. Biochem., 1997.Google Scholar
- 26.M.T. Swain and G.J.L. Kemp. Modelling protein side-chain conformations using constraint logic programming. Computers Chem., in press.Google Scholar
- 29.P. Tuffery, C. Etchebest, S. Hazout, and R. Lavery. A new approach to the rapid determination of protein side-chain conformations. J. Biomol. Struct. Dynam., 8:1267–1289, 1991.Google Scholar
- ]32.Z. Xiang and B. Honig. Extending the accuracy limits of prediction for side-chain conformations. J. Mol. Biol., 2001.Google Scholar