The AQcalc user interface

AQcalc web server have been tested in Firefox and Chrome browsers. It seems to work also with Internet Explorer 11.


  • To cite AQcalc :

    • Maral Afshinpour, Logan A. Smith, and Suvobrata Chakravarty
      AQcalc: A Webserver that Identifies Weak Molecular Interactions in Protein Structures.
      2023. (submitted)


    Submitting your job

    Usage of the AQcalc user interface is straightforward. The main page features a search box, which accepts any valid PDB code. Alternatively, you can provide a PDB file.

    To retrieve a completed job you can use the Session ID search box (top-right corner) and provide the Session ID (i.e. da893bb3-b476-4e91-8589-11f7c186212d).

Algorithm

AQcalc identifies four types of interaction based on the distance and angle cutoff. Criteria for interaction types are explained below.

Interaction Identification

AQcalc utilizes the distance and angle between the anion and ring edges as a criterion to identify AQ interactions. Briefly, for an AQ interaction, the distance between the anion and an aromatic ring atom is ≤4.5 Å and the angle between the distance vector and the ring plane is ≤35.0°. Asp and Glu sidechain carboxylate group atoms and the phosphate group atoms (e.g., OP1 and OP2 in DNA/RNA in PDB, and O9 and O10 DCCP atoms in MemProtMD coordinate files) are the anions and the aromatic residue (Trp, Tyr, and Phe) sidechain ring atoms are the edges. Sidechain-sidechain hydrogen bonded pairs of Asp/Glu and Trp/Tyr (phosphate and Trp/Tyr) are not counted as AQ interactions because these pairs are counted as HBAQ. Hydrogen bonds are calculated using HBPLUS program with the default settings. Because user-defined coordinate files can be uploaded, AQcalc, as default, ignores residues with missing sidechain atoms and considers only the first model of the NMR ensemble structure. For identifying CP interactions, AQcalc utilizes distance (i.e., radius and height of the cylinder perpendicular to the aromatic ring plane). The optimum radius and height of the cylinder were first determined from the distances of the ring center of aromatic cages engulfing methyl-lysine-NZ and methyl-arginine-CZ atoms in high-resolution structures. These distances were then compared with that of lysine-NZ/arginine-CZ atoms and aromatic residue ring center to make sure that the respective distance and radius distribution were very similar. For Arg stacked CP, 2.5 Å≤ hc (cylinder height)≤4.5 Å and radius ≤3.0 Å, while for arginine non-stacked CP, 3.5 Å≤ hc (cylinder height)≤5.5 Å and radius ≤3.0 Å distance are used. For Lys CP, 3.0 Å≤ hc (cylinder height)≤5.0 Å and radius ≤3.0 Å distance are used. The differences with the RING 3.0 server for identifying CP are likely due to the distance criteria. AQcalc considered a salt bridge pair to occur when Lys/Arg side chain atoms are hydrogen bonded to Asp/Glu sidechain or phoshphate oxygen atoms. That is, electrostatically interacting opposite charges that are not hydrogen bonded are not considered here as salt bridges. A group of residues interacting with AQ, CP, HBAQ, and SB is considered a cluster when there is no residue common between the two distinct clusters.

How to use AQcalc (example)

Caveoline-1 (known as membrane-sculpting protein) is a main structural protein of caveolae and specifically bound to cholestrol and play roles in cell migration, signaling, cholestrol distribution and remodeling of membrane in responses to environmental and physiological changes (Yang et al. 2014). Caveoline-1 self-assembly forms highly stable oligimeric domain (OD) is the main region that lead the 8S formation through mediating protomer-protomer interactions (Han et al. 2020). Porta et al (2022) introduced some key interacting residues (R54, E74, A72, H79, W85, W128, I72, V71, A112, G116, and A120) located in different protomer that are involved in 8S formation.

Here we submit CryoEM structure of the Caveoline-1 8S complex (PDB: 7SC0) to the AQCalc.

Weak interaction analysis was performed and main amino acids involved in different types of weak interactions were identified.



Results


PDB Code: 7cs0

Uniq ID: ba39a8c4-6636-436e-be5f-a693428a313b

HBPLUS Hydrogen Bond Calculator v 3.2            Oct 13 19:50:12 UTC 2022  
(c) I McDonald, D Naylor, D Jones and J Thornton 1993 All Rights Reserved.  
  
Configured for 100000 atoms and 24000 residues.  
  
Criteria  
  
Minimum Angles; DHA 90.00, HAAA 90.00, DAAA 90.00  
Maximum Distances; D-A 3.9, H-A 2.5, S-S 3.0  
Maximum angles at aromatic acceptors DAAX 20.00, HAAAX 20.00  
Minimum covalent separation 3 Covalent bonds  
  
  
Processing file "pdb7cs0.ent" . . .  
Opening "pdb7cs0.ent" for protein co-ordinates. . .  
  
 
HBONDED-ANION-PI   GLU-128-A    TRP-155-A     	  104 E  131 W   	 pdb7cs0  
HBONDED-ANION-PI   GLU-128-B    TRP-155-B     	  104 E  131 W   	 pdb7cs0  
  
  
ANION-PI   GLU-106-B    TYR-104-B      3.34    2.95   OE2:GLU:106:B   CD2:TYR:104:B    48.25  	   82 E   80 Y   	 nhb: 2  MS: 0  SS: 2  SB: 2 INTRA  pdb7cs0  
ANION-PI   GLU-106-A    TYR-104-A      3.25    0.65   OE2:GLU:106:A   CD2:TYR:104:A    45.52  	   82 E   80 Y   	 nhb: 2  MS: 0  SS: 2  SB: 2 INTRA  pdb7cs0  
ANION-PI   ASP-177-B    TRP-210-B      3.26   17.08   OD2:ASP:177:B   CD1:TRP:210:B    53.80  	  153 D  186 W   	 nhb: 0  MS: 0  SS: 0  SB: 0 INTRA  pdb7cs0  
ANION-PI   ASP-177-A    TRP-210-A      3.54   20.85   OD2:ASP:177:A   CD1:TRP:210:A    49.81  	  153 D  186 W   	 nhb: 1  MS: 0  SS: 1  SB: 0 INTRA  pdb7cs0  
  
  
CATION-PI  ARG-86-A     TRP-210-A      5.35    2.99    46.23  	   62 R  186 W   	nhb: 5  MS: 0  SS: 2  SB: 2  INTRA  pdb7cs0  
CATION-PI  ARG-35-A     TRP-60-A       2.98    2.73    13.16  	   19 R   36 W   	nhb: 0  MS: 0  SS: 0  SB: 0  INTRA  pdb7cs0  
CATION-PI  ARG-35-B     TRP-60-B       3.16    2.58    10.27  	   18 R   36 W   	nhb: 0  MS: 0  SS: 0  SB: 0  INTRA  pdb7cs0  
CATION-PI  ARG-86-A     TYR-104-A      4.61    0.25    79.27  	   62 R   80 Y   	nhb: 5  MS: 0  SS: 2  SB: 2  INTRA  pdb7cs0  
CATION-PI  ARG-86-B     TYR-104-B      4.53    0.07    81.89  	   62 R   80 Y   	nhb: 5  MS: 0  SS: 2  SB: 2  INTRA  pdb7cs0  
  
AROMATIC-CAGE   	 ARG-86-A     TRP-210-A      5.35   2.99   46.23    pdb7cs0          
AROMATIC-CAGE   	 ARG-86-A     TYR-104-A      4.61   0.25   79.27    pdb7cs0          
  
  
SALTBRIDGE  ASP-113-A   ARG-111-A   2   	   89 D   87 R   	 INTRA  pdb7cs0  
SALTBRIDGE  ASP-113-B   ARG-111-B   2   	   89 D   87 R   	 INTRA  pdb7cs0  
SALTBRIDGE  ASP-125-A   ARG-153-A   2   	  101 D  129 R   	 INTRA  pdb7cs0  
SALTBRIDGE  ASP-125-B   ARG-153-B   2   	  101 D  129 R   	 INTRA  pdb7cs0  
SALTBRIDGE  ASP-144-B   ARG-179-B   1   	  120 D  155 R   	 INTRA  pdb7cs0  
SALTBRIDGE  ASP-178-B   ARG-173-B   1   	  154 D  149 R   	 INTRA  pdb7cs0  
SALTBRIDGE  ASP-190-B   ARG-96-B    1   	  166 D   72 R   	 INTRA  pdb7cs0  
SALTBRIDGE  ASP-203-A   ARG-86-A    2   	  179 D   62 R   	 INTRA  pdb7cs0  
SALTBRIDGE  ASP-203-B   ARG-86-B    2   	  179 D   62 R   	 INTRA  pdb7cs0  
SALTBRIDGE  ASP-53-B    ARG-43-B    1   	   29 D   26 R   	 INTRA  pdb7cs0  
SALTBRIDGE  ASP-61-A    ARG-101-B   1   	   37 D   77 R   	 INTER  pdb7cs0  
SALTBRIDGE  ASP-61-A    ARG-87-B    1   	   37 D   63 R   	 INTER  pdb7cs0  
SALTBRIDGE  ASP-61-B    ARG-101-A   1   	   37 D   77 R   	 INTER  pdb7cs0  
SALTBRIDGE  ASP-61-B    ARG-87-A    2   	   37 D   63 R   	 INTER  pdb7cs0  
SALTBRIDGE  ASP-94-A    ARG-96-A    1   	   70 D   72 R   	 INTRA  pdb7cs0  
SALTBRIDGE  ASP-94-B    ARG-96-B    1   	   70 D   72 R   	 INTRA  pdb7cs0  
SALTBRIDGE  GLU-106-A   ARG-205-A   2   	   82 E  181 R   	 INTRA  pdb7cs0  
SALTBRIDGE  GLU-106-B   ARG-205-B   2   	   82 E  181 R   	 INTRA  pdb7cs0  
SALTBRIDGE  GLU-128-A   ARG-153-A   2   	  104 E  129 R   	 INTRA  pdb7cs0  
SALTBRIDGE  GLU-128-B   ARG-153-B   2   	  104 E  129 R   	 INTRA  pdb7cs0  
SALTBRIDGE  GLU-199-A   ARG-173-A   1   	  175 E  149 R   	 INTRA  pdb7cs0  
SALTBRIDGE  GLU-40-A    ARG-43-A    2   	   24 E   27 R   	 INTRA  pdb7cs0  
SALTBRIDGE  GLU-40-B    ARG-43-B    2   	   23 E   26 R   	 INTRA  pdb7cs0  
  



finished reading all atoms  
finished reading all DNA atom  
finished getting sugar phosphate atoms  
finished getting negatively charged  atoms


His79 and Trp85 form a pocket and cation-pi interactions between basic side chain of Arg54 (located in pin motif (PM)) and aromatic group of Trp85, caused the intercalating of Arg54 in pocket and lead to pin OD domain in place. Mutation of Arg54 to Alanine disrupt the weak interaction between Arg and Trp and prevent formation of 8S complex. In addition, Glu74 form Anion-pi interaction with Trp128 and Tyr100. An arrangement of Phe81 and Trp98 aromatic groups around Arg101 form aromatic-cage structure which is defined by AQcalc.