Binding Affinity Prediction of Protien Ligand Complex containing Zinc-BAPPL-Z Server

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BAPPL–Z server



Carbonic Anhydrase complexed with Ligand and Zinc ion (1cil)


Welcome to the BAPPL-Z server

Binding Affinity Prediction of Protein-Ligand complex containing Zinc [ BAPPL-Z ] server computes the binding free energy of a zinc containing metalloprotein-ligand complex using an all atom energy based empirical scoring function [1], [2] & [3].

BAPPL-Z server provides two methods as options.

Method 1 : Input should be an energy minimized zinc containing metalloprotein-ligand complex, minimized using a dielectric of 1. The input complex should have hydrogens added and protonation states assigned. RESP charges should be assigned to the protein atoms and Mulliken charges to the ligand and the zinc ion. Stote & Karplus van der Waals parameters should be assigned to the zinc ion. Amber and GAFF force field van der Waals parameters should be assigned to the protein and the ligand atoms respectively. The server directly computes the binding affinity of the input complex using the scoring function [1] employing a sigmoidal dielectric for electrostatics I and dielectric of 80 for electrostatics II calculation.

Method 2 : Input should be an energy minimized zinc containing metalloprotein-ligand complex, minimized using a sigmoidal dielectric. The input complex should have hydrogens added and protonation states assigned. RESP charges should be assigned to the protein, ligand and the zinc ion. Stote & Karplus van der Waals parameters should be assigned to the zinc ion. Amber and GAFF force field van der Waals parameters should be assigned to the protein and the ligand atoms respectively. The server directly computes the binding affinity of the input complex using the scoring function [1] employing a sigmoidal dielectric for electrostatics I and II calculation.

For format specifications on the input, please refer to the README file.

For the purpose of validation of the empirical scoring function [1] a dataset of 90 zinc containing metalloprotein-ligand complexes has been prepared. Click here to access the Metalloprotein-Ligand Complex Dataset.
BAPPL-Z server
Select option                                           Method 1            Method 2

           Input PDB file

E-mail address


Instructions for using the server

  1. The input zinc containing metalloprotein-ligand complex should follow the format described in the README file. In case of any differences, either an error is generated resulting in the termination of computation or the predicted binding affinity value will have errors in it.
  2. Please specify the E-mail address.
  3. Browse and select the input file.(The input file name should not contain whitespace(s) & PDBID should be a four letter code, like 1a30.pdb)
  4. Click Submit to get the result.
  5. The Predicted Binding Affinity value will be sent via E-mail at the address specified. The computation may take 5-10 minutes depending upon the load on the web server and the number of atoms in the input file.
   IMPORTANT

          The predicted binding affinities are dependent upon:
  • The protonation states assigned to the ligand and the protein atoms.
  • The procedure used to derive the partial atomic charges for the ligand atoms and the zinc ion like (AM1-BCC, HF/6-31G* etc.) and the force field used to assign the partial atomic charges for the protein atoms like (AMBER, CHARMM, OPLS, etc.).
  • The force field used to assign the van der Waals parameters for the ligand and protein atoms and the zinc ion.
  • Energy minimization / geometry optimization protocol used to remove any clashes from the complex.
REFERENCES
[1] Jain, T. and Jayaram, B. A computational protocol for predicting the binding affinities of zinc containing metalloprotein-ligand complexes. PROTEINS: Struct. Funct. Bioinfo., 2007, 67, 1167-1178. [Abstract]  [BAPPL server]
[2] Jain, T. and Jayaram, B. (2005) An all atom energy based computational protocol for predicting binding affinities of protein-ligand complexes. FEBS Letters, 579, 6659-6666. [Abstract]  [BAPPL server]
[3] Arora, N. and Jayaram, B. (1998) Energetic of base pairs in B-DNA in solution: An appraisal of potential functions and dielectric treatments. J. Phys. Chem. B. 102, 6139-6144. [Abstract]
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