Molecular Docking of  (R)-2,3-dichloro-1-propanol (R-DCL) 
to DhaA.Cl- Complex by AUTODOCK

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Date: 9.11.04 - 16.11.04
Author: Klvana, M.

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Motivation: 

•	Preparation of DhaA.Cl-.R-DCL complex that will be used for random expulsion molecular dynamics (REMD) simulation parallel to or instead of DhaA.Cl-.S-DCL.

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Methods:

•	List of Programmes and Scripts: PYMOL 0.97 (DeLano Scientific, San Diego, USA), WHATIF 5.0 (Vriend, G., 1990), AUTODOCK 3.05 (Morris et al., 1998), q.kollua and addsol;

•	Procedure: Rotatable bonds and small molecular centre were assigned for R-DCL using Autotors. R-DCL has three such bonds (C1-O, C1-C2 and C2-C3). 1CQWA_ncimb was used as DhaA structure. The DhaA was modified by addition of polar hydrogens by WHATIF, partial atomic charges using the script q.kollua and solvation parameters by the script addsol. Halide was taken from the crystal structure but changed from iodide to chloride with charge of -1. Since there is no chlorine atomic type for protein structure in AUTODOCK chloride was represented by X atom type with well depth and non-bonded parameters of chlorine. Electrostatic and atomic (C, O, H and Cl) maps (81x81x81 points and grid spacing of 0.25 Å) were calculated using Autogrid. Centre of each grid was set to Cg of H272. Fifty docking runs DhaA.Cl- were performed for TCP and DCL. A Lamarckian genetic algorithm was used with an initial population size of 50 individuals. A maximum of 1.5x106 number of energy evaluations and a maximum number of 27 000 generation served as termination criteria for each docking run. Elitism was set to 1, mutation rate to 0.02 and crossover rate to 0.8. A local search based on a pseudo-Solis and Wets algorithm (with a maximum of 300 iteration per local search) was applied with probability of 0.06 of performing the local search on an individual. Final orientations from every docking were clustered with a clustering tolerance for the root-mean-square positional deviation of 0.5 Å. 

Results and Discussion:

•	Docking of R-DCL to DhaA.Cl- complex provided only one cluster of all 50 orientations (R-DCL01s; Table 1). R-DCL01s was bound closely to chloride anion. Orientation of CH2OH group is very similar to that of S-DCL2a (from docking of S-DCL to 1CQWA_ncimb) which was selected for REMD. Cl10 of R-DCL is oriented toward slot; Cl10 of S-DCL toward main tunnel (Figure 1).

Table 1. Docking of R-DCL to 1CQWA_ncimb.
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   Clusters      Orientations       Docked Energy (A, B)
   - Name -       - Number -           - kcal/mol -    
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   R-DCL01s           50           -4.77 [-5.41, +0.64]
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	A = intermolecular energy, B = internal energy of ligand

 
Figure 1. Docked S-DCL (slate) and R-DCL (red) in 1CQWA_ncimb.Cl-.

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Conclusions:

•	Following REMD study can be conducted with both 1CQWA_ncimb.Cl-.S-DCL and 1CQWA_ncimb.Cl-.R-DCL complexes (Figure 1). The latter complex will be preferred.

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Data:

•	Protein structure (1CQWA_ncimb.pdb):
	klvanamn@cronus:/home/klvanamn/DATA/STR/PROT/DhaA
	martink@eldar.chemi.muni.cz:/home/data/martink/STR/PROT/DhaA
	(PROT = Protein)

•	Molecular docking of R-DCL to 1CQWA_ncimb.Cl-:
	klvanamn@cronus:/home/klvanamn/DATA/DOCK/DhaA/1CQWA_ncimb.Cl/
	/R-DCL
	martink@eldar.chemi.muni.cz:/home/data/martink/DOCK/DhaA/1CQWA_ncimb.Cl/
	/R-DCL

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References:

•	Morris, G.M., Goodsell, D. S., Huey, R., Hart, W. E., Halliday, R. S., Belew, R. K., and Olson, A. J. (1998), Journal of Computational Chemistry 19, 1639-1662.

•	Vriend, G. (1990) Journal of Molecular Graphics 8, 52-56.