Hbind -- Identifying hydrogen bonds by donor/acceptor chemistry and geometric constraints
Software to rigorously define intermolecular H-bonds by donor/acceptor chemistry and geometric constraints, which was developed, used, and described in detail in
- Raschka, Sebastian, Alex Wolf, Joseph Bemister‐Buffington, and Leslie A. Kuhn (2018) “Protein-ligand interfaces are polarized: discovery of a strong trend for intermolecular hydrogen bonds to favor donors on the protein side with implications for predicting and designing ligand complexes” Journal of Computer-Aided Molecular Design. Journal of Computer-Aided Molecular Design (accepted manuscript) [biorxiv preprint]
Code Repository: https://github.com/psa-lab/Hbind
Documentation: https://psa-lab.github.io/Hbind
[Interactions between an PKCI-substrate analog (1KPF) with its ligand (adenosine monophsophate) via HbindViz and PyMOL; hydrogen atoms not shown]
Installation
Installing Hbind requires Perl and the GCC compiler, both of which come pre-installed with most Unix- and Linux-based operating systems.
To install Hbind, simply download this repository, unpack it, and navigate into the main Hbind folder. Then, execute the following command in your terminal:
perl install_hbind.plUpon successful installation, the Hbind software will be ready to use from the bin/ subdirectory. To show the help and usage menu execute execute the following command in your terminal:
./bin/hbind -hHBIND Version: 1.0.0
Documentation: http://psa-lab.github.io/Hbind
Raschka, Wolf, Bemister-Buffington, Kuhn (2018)
Protein Structure and Analysis Lab, MSU (http://kuhnlab.bmb.msu.edu)
USAGE:
-p STRING Path to protein PDB file
-l STRING Path to ligand mol2 file (in docked conformation)
-s Include saltbridges in the output
-t Include a summary table in the outputPlease see the "Usage" section below for more information on how to use Hbind.
Usage
To execute Hbind, please navigate to its main directory from where you installed it and run the following command to identify the hydrogen bonds in a protein ligand interface:
./bin/hbind -p ./example_files/1KPF.pdb \
-l ./example_files/1KPF_AMP.mol2 Here, 1KPF.pdb is an excerpt from the PDB structure 1KPF (PKCI-substrate analog) with its ligand 1KPF_AMP.mol2 (adenosine monophsophate). The structures are provided in Hbind's subdirectory "example_files/".
Before you run Hbind, please make sure that you provide the protein structure in PDB format and the ligand structure in MOL2 format, and please ensure that the ligand's protonation state (hydrogen assignment) is correct.
To protonate a ligand, tools such as OpenEye MolCharge can be used. However, it is recommended to protonate a ligand in presence of its protein environment, for example, by using tools such as What If or Yasara OptHyd.
After running the command from the beginning of this section, the following output should be displayed:
HBIND Version: 1.0.0
Documentation: http://psa-lab.github.io/Hbind
Raschka, Wolf, Bemister-Buffington, Kuhn (2018)
Protein Structure and Analysis Lab, MSU (http://kuhnlab.bmb.msu.edu)
Ligand file: /Users/sebastian/code/hbind/example_files/1KPF_AMP.mol2
Protein file: /Users/sebastian/code/hbind/example_files/1KPF.pdb
++++++++++++++++++++++++++++++++ HBind Interaction Table ++++++++++++++++++++++++++++++++
# | Ligand Atom -- Protein Atom | Bond D-H-A Lig.-Prot.
# | # TYPE -- RES CH_ID RES_NO A_TYPE | DIST. ANGLE INTERACTION
| hbond 1 2 O.2 -- ASN A 99 ND2 2.911 174.0 Acceptor - Donor
| hbond 2 3 O.3 -- SER A 107 N 2.802 166.8 Acceptor - Donor
| hbond 3 3 O.3 -- VAL A 108 N 3.031 178.8 Acceptor - Donor
| hbond 4 4 O.3 -- HIS A 112 NE2 2.593 163.1 Acceptor - Donor
| hbond 5 4 O.3 -- HIS A 114 NE2 2.581 140.4 Acceptor - Donor
| hbond 6 10 O.3 -- ASP A 43 OD2 2.714 167.1 Donor - Acceptor
| hbond 7 12 O.3 -- ASP A 43 OD1 2.607 154.1 Donor - Acceptor
| hbond 8 22 N.ar -- ILE A 44 N 3.156 154.9 Acceptor - DonorTo include salt bridges in the listing, you can use the -s option as shown below:
./bin/hbind -p ./example_files/1KPF.pdb \
-l ./example_files/1KPF_AMP.mol2 -sHBIND Version: 1.0.0
Documentation: http://psa-lab.github.io/Hbind
Raschka, Wolf, Bemister-Buffington, Kuhn (2018)
Protein Structure and Analysis Lab, MSU (http://kuhnlab.bmb.msu.edu)
Ligand file: /Users/sebastian/code/hbind/example_files/1KPF_AMP.mol2
Protein file: /Users/sebastian/code/hbind/example_files/1KPF.pdb
++++++++++++++++++++++++++++++++ HBind Interaction Table ++++++++++++++++++++++++++++++++
# | Ligand Atom -- Protein Atom | Bond D-H-A Lig.-Prot.
# | # TYPE -- RES CH_ID RES_NO A_TYPE | DIST. ANGLE INTERACTION
| hbond 1 2 O.2 -- ASN A 99 ND2 2.911 174.0 Acceptor - Donor
| hbond 2 3 O.3 -- SER A 107 N 2.802 166.8 Acceptor - Donor
| hbond 3 3 O.3 -- VAL A 108 N 3.031 178.8 Acceptor - Donor
| hbond 4 4 O.3 -- HIS A 112 NE2 2.593 163.1 Acceptor - Donor
| hbond 5 4 O.3 -- HIS A 114 NE2 2.581 140.4 Acceptor - Donor
| hbond 6 10 O.3 -- ASP A 43 OD2 2.714 167.1 Donor - Acceptor
| hbond 7 12 O.3 -- ASP A 43 OD1 2.607 154.1 Donor - Acceptor
| hbond 8 22 N.ar -- ILE A 44 N 3.156 154.9 Acceptor - Donor
| saltb 1 2 O.2 -- HIS A 114 NE2 4.245 N/A Acceptor - Donor
| saltb 2 3 O.3 -- HIS A 112 NE2 3.382 N/A Acceptor - Donor
| saltb 3 4 O.3 -- HIS A 114 ND1 4.462 N/A Acceptor - Donor
| saltb 4 10 O.3 -- ASP A 43 OD1 3.395 N/A Donor - Acceptor
| saltb 5 12 O.3 -- ASP A 43 OD2 3.607 N/A Donor - AcceptorFor additional information, i.e. a summary talbe that includes the number of hydrophobic contacts or SLIDE docking scores, provide the -t flag:
./bin/hbind -p ./example_files/1KPF.pdb \
-l ./example_files/1KPF_AMP.mol2 -s -tHBIND Version: 1.0.0
Documentation: http://psa-lab.github.io/Hbind
Raschka, Wolf, Bemister-Buffington, Kuhn (2018)
Protein Structure and Analysis Lab, MSU (http://kuhnlab.bmb.msu.edu)
Ligand file: /Users/sebastian/code/hbind/example_files/1KPF_AMP.mol2
Protein file: /Users/sebastian/code/hbind/example_files/1KPF.pdb
+++++++++++++++++ Summary +++++++++++++++++++
| Protein-Ligand Hydrophobic Contacts : 39
| Protein-Ligand H-bonds : 8
| Protein-Ligand Salt-bridges : 5
| Metal-Ligand Bonds : 0
| SLIDE OrientScore : -8.787
| SLIDE AffiScore (heavy atoms) : -0.102
| SLIDE AffiScore : -7.557
++++++++++++++++++++++++++++++++ HBind Interaction Table ++++++++++++++++++++++++++++++++
# | Ligand Atom -- Protein Atom | Bond D-H-A Lig.-Prot.
# | # TYPE -- RES CH_ID RES_NO A_TYPE | DIST. ANGLE INTERACTION
| hbond 1 2 O.2 -- ASN A 99 ND2 2.911 174.0 Acceptor - Donor
| hbond 2 3 O.3 -- SER A 107 N 2.802 166.8 Acceptor - Donor
| hbond 3 3 O.3 -- VAL A 108 N 3.031 178.8 Acceptor - Donor
| hbond 4 4 O.3 -- HIS A 112 NE2 2.593 163.1 Acceptor - Donor
| hbond 5 4 O.3 -- HIS A 114 NE2 2.581 140.4 Acceptor - Donor
| hbond 6 10 O.3 -- ASP A 43 OD2 2.714 167.1 Donor - Acceptor
| hbond 7 12 O.3 -- ASP A 43 OD1 2.607 154.1 Donor - Acceptor
| hbond 8 22 N.ar -- ILE A 44 N 3.156 154.9 Acceptor - Donor
| saltb 1 2 O.2 -- HIS A 114 NE2 4.245 N/A Acceptor - Donor
| saltb 2 3 O.3 -- HIS A 112 NE2 3.382 N/A Acceptor - Donor
| saltb 3 4 O.3 -- HIS A 114 ND1 4.462 N/A Acceptor - Donor
| saltb 4 10 O.3 -- ASP A 43 OD1 3.395 N/A Donor - Acceptor
| saltb 5 12 O.3 -- ASP A 43 OD2 3.607 N/A Donor - Acceptor
Hydrogen bond rules
Hbind's rules for identifying hydrogen bonds protein-ligand interfaces are based on the criteria by Ippolito et al. [1] and McDonald and Thornton [2].
Hydrogen bond criteria:
- Hydrogen to acceptor distance: 1.5-2.5 Å
- Donor to acceptor distance: 2.4-3.5 Å
- Donor-H-acceptor angle (θ): 120-180°
- Pre-acceptor–acceptor–H angle (φ): 90-180°
(Hydrogen bonds must meet all of these criteria.)
Criteria for metal interactions:
- Lone pair atom distance to K or Na: 2.0-2.9 Å
- Lone pair atom distance to Ca, Co, Cu, Fe, Mg, Mn, Ni, or Zn: 1.7-2.6 Å
Additional command line options are available to list longer-range salt bridge interactions (up to 4.5 Å) and the number of hydrophobic contancts between protein and ligand atoms.
[1] Ippolito, Joseph A, Richard S Alexander & David W Christianson. 1990. Hydrogen bond stereo-chemistry in protein structure and function. Journal of Molecular Biology 215(3). 457–471.
[2] McDonald, Ian & Janet M Thornton. 1994. Atlas of side-chain and main-chain hydrogen bonding. http://www.biochem.ucl.ac.uk/bsm/atlas: Biochemistry and Molecular Biology Department, University College London.
Hbind tools
Protein Recognition Index (PRI)
Software for assessing the native-likeness of designed or predicted protein-ligand interfaces, which can be used to guide protein mutagenesis and ligand design.
Hbind Interaction Viz
A program for creating PyMOL H-bond interaction views from Hbind tables.