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Time-efficient docking of flexible ligands into active sites of proteins

Technical Report ·
OSTI ID:401858
; ;  [1]
  1. Inst. for Algorithms and Scientific Computing, Sankt Augustin (Germany)

We present an algorithm for placing flexible molecules in active sites of proteins. The two major goals in the development of our. docking program, called FlexX, are the explicit exploitation of molecular flexibility of the ligand and the development of a model of the docking process that includes the physico-chemical properties of the molecules. The algorithm consists of three phases: The selection of a base fragment, the placement of the base fragment in the active site, and the incremental construction of the ligand inside the active site. Except for the selection of the base fragment, the algorithm runs without manual intervention. The algorithm is tested by reproducing 11 receptor-ligand complexes known from X-ray crystallography. In all cases, the algorithm predicts a placement of the ligand which is similar to the crystal structure (about 1.5 {Angstrom} RMS deviation or less) in a few minutes on a workstation, assuming that the receptor is given in the bound conformation.

Research Organization:
Stanford Univ., CA (United States)
OSTI ID:
401858
Report Number(s):
CONF-9507246--
Country of Publication:
United States
Language:
English

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