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BAPPL server


HIV-I Protease complexed with U75875 (1hiv.pdb)



Welcome to the BAPPL server

Binding Affinity Prediction of Protein-Ligand (BAPPL) server computes the binding free energy of a non-metallo protein-ligand complex using an all atom energy based empirical scoring function [1] & [2].


BAPPL server provides two methods as options:

Method 1 : Input should be an energy minimized protein-ligand complex with hydrogens added, protonation states, partial atomic charges and van der Waals parameters (R* and ε) assigned for each atom. The server directly computes the binding affinity of the complex using the assigned parameters. For format specifications on the input, please refer to the README file.

Method 2 : Input should be an energy minimized protein-ligand complex with hydrogens added and protonation states assigned. The net charge on the ligand should be specified. The server derives the partial atomic charges of the ligand using the AM1-BCC procedure [3] and GAFF [5] force field for van der Waals parameters. Cornell et al. force field [4] is used to assign partial atomic charges and van der Waals parameters for the proteins. 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 161 non-metallo protein-ligand complexes has been prepared. Click here to access the Protein-Ligand Complex Dataset.


BAPPL server
Select Option
                                    Method 1
                                    Method 2    Net Ligand Charge


          Input PDB file

E-mail address



Instructions for using the server

  1. The input protein-ligand complex should follow the format described in the README files. 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, Name and Institution.
  3. Choose either one of the options : "Method 1" OR "Method 2"
  4. For Method 2, specify the Net ligand charge.
  5. 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)
  6. Click Submit to get the result.
  7. 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 protein atoms.
  • The procedure used to derive the partial atomic charges for ligand atoms like (AM1-BCC, HF/6-31G*/RESP, 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 ligand and protein atoms.
  • Energy minimization / geometry optimization protocol used to remove any clashes from the complex.
NOTE : The empirical scoring function [1] has been calibrated using the HF/6-31G*/RESP equivalent partial atomic charges and Cornell et al. [4] and GAFF [5] force field parameters for proteins and ligands respectively. We have provided the AM1-BCC procedure for deriving partial atomic charges of ligands for Method 2 because this procedure is fast and produces charges of comparable accuracy to the HF/6-31G*/RESP method.

REFERENCES
[1] 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]
[2] 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]
[3] Jakalian, A., Bush, B.L., Jack, D.B. and Bayaly, C.I. (2000) Fast, efficient generation of high-quality atomic charges. J. Comput. Chem. 21, 132-146.
[4] Cornell, W.D. et al. (1995) A second generation force field for the simulation of proteins, nucleic acids and organic molecules. J. Am. Chem. Soc. 117, 5179-5197.
[5] Wang, J., Wolf, R.M., Caldwell, J.W., Kollman, P.A. and Case, D.A. (2004) Development and testing of a general amber force field. J. Comput. Chem. 25, 1157-1174.
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