What is MolSurfer?

Description

Molsurfer is based on JSMol and replaces the former java based software. It uses the representation of the macromolecular interface generated by adsi (the interface module of ads, analytically defined molecular surfaces ) and JSmol, a JavaScript implementation of Jmol. (Java plugins have recently become very restrictive, due to many security concerns.)

It can be used to study protein-protein and protein-DNA/RNA interfaces. The 2D projections of the computed interface aid visualization of complicated interfacial geometries in 3D. Molecular properties, including hydrophobicity and electrostatic potential, can be projected onto the interface. MolSurfer can thereby aid exploration of molecular complementarity, identification of binding "hot spots" and prediction of the effects of mutations. MolSurfer can also facilitate the location of cavities at macromolecular interfaces.

Links to MolSurfer

You can generate links to molsurfer, allowing the analysis of interfaces in RCSB entries. For this the URL parameters pdbidinput, chainid1 and chainid2 needs to be specified in the following manner:

http://molsurfer.h-its.org/cgi-bin/molsurfer_master.cgi?pdbidinput=1hbb&chainid1=A&chainid2=B,C,D

Just replace the bold parts of the URL above with the information about your PDB entry.

Details of Interface Mapping and Displayed Properties

  • A quasi rectangular mesh with 1 Å spacing was generated on the analytically defined interface between these 2 macromolecules.
  • Points for which the sum of the distances to the closest atoms of macromolecule I and II exceeds 6 Å were deleted.
  • Heteroatoms that lie within 3 Å of any interface point were added.
  • The properties of each macromolecule were projected onto every point of the interface; these are the properties assigned to the closest atom to the point.
  • Residue hydrophobicities were assigned according to the residue name and following the parameters in Eisenberg D., Weiss R.M., Terwilliger T.C. and Wilcox W. (1982) Farad. Symp. Chem. Soc., 17, 109-120, namely:

  •   ALA   0.25       GLN  -0.69       LEU   0.53       SER  -0.26
      ARG  -1.80       GLU  -0.62       LYS  -1.10       THR  -0.18
      ASN  -0.64       GLY   0.16       MET   0.26       TRP   0.37
      ASP  -0.72       HIS  -0.40       PHE   0.61       TYP   0.02
      CYS   0.04       ILE   0.73       PRO  -0.07       VAL   0.54
      none of the above                 0.00
  • Atomic hydrophobicities were assigned according to the atom name and follow  Eisenberg D., Wesson M., Yamashita M. (1989) Chem. Scrip., 29A, 217-221, namely:

  •   'NZ  LYS'  -38       'OE1 GLU'  -37         'C'    18
      'NH1 ARG'  -38       'OE2 GLU'  -37         'S'     5
      'NH2 ARG'  -38       'OD1 ASP'  -37         'O'    -9
                           'OD2 ASP'  -37         'N'    -9
      none of the above    0
  • Atomic radii were also assigned from the previous reference, namely:

  •   'C'    1.9 A
      'S'    1.8 A
      'O'    1.4 A
      'N'    1.7 A
      none of the above    1.9 A
  • Electrostatic potential of each (isolated) macromolecule was computed with the APBS program and the potential values were interpolated at each interface point.
  • Additionally, the changes in binding free energy upon alanine mutation were assigned to each side-chain atom of the corresponding residue.  This data can be obtained from the Alanine Scanning Energetics database for example.
  • More details can be found in Analytically Defined (molecular) Surfaces website. The standalone version of MolSurfer can be downloaded from the previous MolSurfer website.

References

  • R.R. Gabdoulline, R.C. Wade & D. Walther (2003) MolSurfer: a macromolecular interface navigator, Nucleic Acids Research, 31, 3349-3351. abstract and full text
  • R.R. Gabdoulline, R.C. Wade & D. Walther. (1999) MolSurfer: two dimensional maps for navigating three-dimensional structures of proteins, Trends Biochem. Sci., 24, 285-287 . (excerpt)
  • N.A. Baker, et al. (2001) Electrostatics of nanosystems: application to microtubules and the ribosome, Proceedings of the National Academy of Sciences, 98, 10037-10041.

Application Examples

MolSurfer applications citing the first reference above.

other examples:
  • Hough MA, Hall JF, Kanbi LD, Hasnain SS. (2001) Structure of the M148Q mutant of rusticyanin at 1.5 angstrom: a model for the copper site of stellacyanin, Acta Crystallogr D, 57, 355-360.
  • Luedemann SK, Gabdoulline RR, Lounnas V, Wade RC, Substrate access to cytochrome P450cam investigated by molecular dynamics simulations: An interactive look at the underlying mechanisms, Internet. J. Chem. (2001) 4, 6. (abstract)
  • Campbell JD, Biggin PC, Baaden M, Sansom MSP (2003) Extending the structure of an ABC transporter to atomic resolution: Modeling and simulation studies of MsbA, Biochemistry, 42 (13), 3666-3673.
  • Flaus A, Rencurel C, Ferreira H, Wiechens N, Owen-Hughes T (2004) Sin mutations alter inherent nucleosome mobility, EMBO Journal, 23, 343-353.
  • Wang T, Tomic S, Gabdoulline RR, Wade RC (2004) How optimal are the binding energetics of barnase and barstar? Biophys J. 87, 1618-30.
  • Huelsmeyer M, Chames P, Hillig RC, Stanfield RL, Held G, Coulie PG, Alings C, Wille G, Saenger W, Uchanska-Ziegler B, Hoogenboom HR, Ziegler A, (2005) A Major Histocompatibility Complex Peptide-restricted Antibody and T Cell Receptor Molecules Recognize Their Target by Distinct Binding Modes (A Major Histocompatibility Complex Peptide-restricted Antibody and T Cell Receptor Molecules Recognize Their Target by Distinct Binding Modes), J. Biol. Chem. 280, 2972-2980.
  • K�vesi I, Schay G, Yonetani T, Laberge M, Fidy J, (2005) High pressure reveals that the stability of interdimeric contacts in the R- and T-state of HbA is influenced by allosteric effectors: Insights from computational simulations, Biochim Biophys Acta, 1764, 516-21.

MolSurfer Example Usage

MolSurfer Usage

MolSurfer can used in three different ways. This mainly differs by the starting parameters used to launch MolSurfer:

Molsurfer analysis using PDB identifier as input

The default input form for Molsurfer allows the input of a PDB identifier together with two sets of chain ID's as can be seen on the following screenshot.


As soon as you enter a valid PDB ID, the search panel shows the title of the respective entry as well as the available chain IDs for this entry.

You need to select two groups of macromolecules in the entry fields for the chain id. Molsurfer will then calculate the properties of the interface between these two groups of molecules.

Starting with PDB IDs does not allow to calculate electrostatic potentials. For this you will need to calculate the corresponding PQR files for the group of macromolecules yourself and use the input that allows the upload of PQR files, see below.

Molsurfer Analysis using PDB file(s) as input

You can also analyse your own PDB files. For this, the chains that form the interface you are interested can be in a single file or in two files. The input for allows you to select between the upload of one or two files. In case you select one file, you also need to give the group of chain IDs, that form the interface, just like in the input form for the PDB ID above.

As example, you can download the following two PDB files: 1AIQ_A.pdb

and 1AIQ_B.pdb and select them in the input form.

Pressing the button: Generate Map will execute the analysis. If you also want to compute electrostatic properties, please continue here.

Molsurfer Analysis including electrostatic properties

]To also calculate electrostatic potentials on the interface, you need to also upload PQR files, that correspond to the group of macromolecules that form the interface you are interested in. You can use the PDB2PQR server to calculate these files.

Since the electrostatic potential is different for the molecules on the two sides of the interface, you need to calculate two PQR files, that correspond to your selection of macromolecules that form the interface of interest.

As an example, extending the example above, you can download the 1AIQ_A.pqr and 1AIQ_B.pqr file and use it for an example calculation. The corresponding input form is shown below.

Display the analysis result

All three input methods will be started by pressing the "Generate Map" button. The result shows on the left 2D maps of the interface with selected properties like On the right you get a 3D view of the interface in a JSMol display. The currently selected property is color mapped to the displayed interface in the 3D structure display. You can modify the 3D display via the menu on the website, or via the context menu of the JSMol display (right click on the structure display). An example display is shown below.

You can explore the interace using the mouse. Corresponding positions on all 2D maps will be shown as well as on the 3D structure view.




MolSurfer Demonstration Cases

The original MolSurfer distribution from 1999 included demonstration cases for 35 protein-protein interfaces as well as 75 protein-DNA/RNA interfaces. These original calculations are offered here as demonstration cases.

They include calculated electrostatic properties.

CodeMolecule 1Molecule 2ProSat+ link
1acbALPHA-CHYMOTRYPSINEglin CProSAT+
1atnACTINDEOXYRIBONUCLEASE IProSAT+
1bqlHYHEL-5 FAB (HEAVY CHAIN)BOBWHITE QUAIL LYSOZYMEProSAT+
1brsBARNASEBARSTARProSAT+
1choALPHA-CHYMOTRYPSIN ATURKEY OVOMUCOID THIRD DOMAIN (OMTKY3)ProSAT+
1cseSUBTILISIN CARLSBERGEGLIN CProSAT+
1dvfFV D1.3FV E5.2ProSAT+
1fbiIGG1 F9.13.7 FAB (HEAVY CHAIN)GUINEA FOWL LYSOZYMEProSAT+
1fc2IMMUNOGLOBULIN FCFRAGMENT B OF PROTEIN A COMPLEXProSAT+
1fdlIGG1-KAPPA D1.3 FAB (HEAVY CHAIN)HEN EGG WHITE LYSOZYMEProSAT+
1glaGLYCEROL KINASEGLUCOSE-SPECIFIC PROTEIN IIIGlcProSAT+
1hwgGROWTH HORMONEGROWTH HORMONE BINDING PROTEINProSAT+
1jhlIGG1-KAPPA D11.15 FV (HEAVY CHAIN)PHEASANT EGG WHITE LYSOZYMEProSAT+
1jrhANTIBODY A6INTERFERON-GAMMA RECEPTOR ALPHA CHAINProSAT+
1lpaLIPASECOLIPASEProSAT+
1mahACETYLCHOLINESTERASEFASCICULIN 2ProSAT+
1mlcIGG1-KAPPA D44.1 FAB (HEAVY CHAIN)HEN EGG WHITE LYSOZYMEProSAT+
1ncaINFLUENZA A SUBTYPE N9 NEURAMINIDASEIGG2A-KAPPA NC41 FAB (HEAVY CHAIN)ProSAT+
1ppfHUMAN LEUKOCYTE ELASTASETURKEY OVOMUCOID INHIBITOR (OMTKY3)ProSAT+
1tabTRYPSINBOWMAN-BIRK TYPE PROTEINASE INHIBITORProSAT+
1tecTHERMITASEEGLIN CProSAT+
1tgsTRYPSINOGENPANCREATIC SECRETORY TRYPSIN INHIBITOR (KAZAL TYPE)ProSAT+
1tpaANHYDRO-TRYPSINBOVINE PANCREATIC TRYPSIN INHIBITORProSAT+
1vfbIGG1-KAPPA D1.3 FV (HEAVY CHAIN)HEN EGG WHITE LYSOZYMEProSAT+
1yqvHyHEL-5 Antibody Heavy ChainHen Egg White LysozymeProSAT+
2kaiKALLIKREIN ABOVINE PANCREATIC TRYPSIN INHIBITORProSAT+
2pcbCYTOCHROME C PEROXIDASE (CCP)CYTOCHROME CProSAT+
2ptcBETA-TRYPSINTRYPSIN INHIBITORProSAT+
2secSUBTILISIN CARLSBERGEGLIN CProSAT+
2sicSUBTILISIN BPN'STREPTOMYCES SUBTILISIN INHIBITOR (SSI)ProSAT+
2sniSUBTILISIN NOVOCHYMOTRYPSIN INHIBITOR 2ProSAT+
2tgpTRYPSINOGENTRYPSIN INHIBITORProSAT+
2tpiTRYPSIN INHIBITORProSAT+
3hfmHYHEL-10 IGG1 FAB (HEAVY CHAIN)HEN EGG WHITE LYSOZYMEProSAT+
3hhrHUMAN GROWTH HORMONEHUMAN GROWTH HORMONE RECEPTOR (hGHbp)ProSAT+
3sgbPROTEINASE B (SGPB)TURKEY OVOMUCOID INHIBITOR (OMTKY3)ProSAT+
4cpaMETALLOCARBOXYPEPTIDASE INHIBITORProSAT+
4insINSULIN (CHAIN B)INSULIN (CHAIN B)ProSAT+
4sgbSERINE PROTEINASE BPOTATO INHIBITOR, PCI-1ProSAT+
4tpiBOVINE PANCREATIC TRYPSIN INHIBITORProSAT+
6rlxRELAXIN, B-CHAINRELAXIN, B-CHAINProSAT+
1a3qPROTEIN (NUCLEAR FACTOR KAPPA-B P52)DNA (5'-D(*GP*GP*GP*GP*AP*TP*TP*CP*CP*CP*C)-3')ProSAT+
1aayPROTEIN (ZIF268 ZINC FINGER PEPTIDE)DNA (5'-D(*TP*AP*CP*GP*CP*CP*CP*AP*CP*GP*C)-3')ProSAT+
1an2ProSAT+
1an4PROTEIN (UPSTREAM STIMULATORY FACTOR)DNA (5'-D(*GP*TP*GP*TP*AP*GP*GP*CP*CP*AP*CP*GP*TP*GP*AP*CP*C P*GP*GP*GP*T)-3')ProSAT+
1aplPROTEIN (MAT-ALPHA2 HOMEODOMAIN)DNA (5'-D(*TP*GP*CP*GP*TP*GP*TP*AP*AP*AP*TP*GP*AP*AP*TP*TP*A P*CP*AP*TP*G)-3')ProSAT+
1bpyPROTEIN (DNA POLYMERASE BETA)DNA (5'-D(*GP*TP*CP*GP*G)-3')ProSAT+
1brnPROTEIN (BARNASE (E.C.3.1.27.-))DNA (5'-D(*CP*GP*AP*C)-3')ProSAT+
1cdwPROTEIN (TATA BINDING PROTEIN (TBP))DNA (5'-D(*CP*AP*GP*CP*CP*TP*TP*TP*TP*AP*TP*AP*GP*CP*AP*G)-3')ProSAT+
1cmaPROTEIN (MET REPRESSOR)DNA (5'-D(*AP*GP*AP*CP*GP*TP*CP*TP*A)-3')ProSAT+
1dnkPROTEIN (DEOXYRIBONUCLEASE I (DNASE I) (E.C.3.1.21.1))DNA (5'-D(*GP*GP*TP*AP*TP*AP*CP*C)-3')ProSAT+
1eriPROTEIN (ECO RI ENDONUCLEASE (E.C.3.1.21.4))DNA (5'-D(*TP*CP*GP*CP*GP*AP*AP*TP*TP*CP*GP*CP*G)-3')ProSAT+
1fjlPAIRED PROTEINDNA (5'-D(*TP*GP*TP*AP*AP*TP*CP*AP*GP*AP*TP*TP*AP*T)-3')ProSAT+
1fokPROTEIN (FOKI RESTRICTION ENDONUCLEASE)DNA (5'-D(*AP*TP*GP*AP*CP*TP*AP*GP*CP*GP*TP*TP*AP*TP*CP*AP*T P*CP*CP*G)-3')ProSAT+
1fosC-JUN PROTO-ONCOGENE PROTEINDNA (5'-D(*TP*TP*CP*TP*CP*CP*TP*AP*TP*GP*AP*CP*TP*CP*AP*TP*CP*CP*AP*T)-3')ProSAT+
1hddPROTEIN (ENGRAILED HOMEODOMAIN)DNA (5'-D(*AP*TP*TP*AP*GP*GP*TP*AP*AP*TP*TP*AP*CP*AP*TP*GP*G P*CP*AP*AP*A)-3')ProSAT+
1hloPROTEIN (TRANSCRIPTION FACTOR MAX)DNA (5'-D(*AP*CP*CP*AP*CP*GP*TP*GP*GP*TP*G)-3')ProSAT+
1hutALPHA-Thrombin heavy chainDNA 5'-D(*GP*GP*TP*TP*GP*GP*TP*GP*TP*GP*GP*TP*TP*GP*G)-3'ProSAT+
1jmcPROTEIN (REPLICATION PROTEIN A (RPA))DNA (5'-D(*CP*CP*CP*CP*CP*CP*CP*C)-3')ProSAT+
1klnPROTEIN (DNA POLYMERASE I KLENOW FRAGMENT (E.C.2.7.7.7))DNA (5'-D(*GP*CP*CP*TP*CP*GP*CP*GP*GP*CP*GP*GP*C)-3')ProSAT+
1latGLUCOCORTICOID RECEPTORDNA (5'-D(*TP*TP*CP*CP*AP*GP*AP*AP*CP*AP*TP*GP*TP*TP*CP*TP*G P*GP*A)-3')ProSAT+
1mdyPROTEIN (MYOD BHLH DOMAIN)DNA (5'-D(*TP*CP*AP*AP*CP*AP*GP*CP*TP*GP*TP*TP*GP*A)-3')ProSAT+
1meyCONSENSUS ZINC FINGERDNA (5'-D(*TP*AP*GP*TP*TP*CP*TP*GP*CP*CP*TP*(C38)P*A)-3')ProSAT+
1mhtPROTEIN (HHAI METHYLTRANSFERASE)DNA (5'-D(*TP*GP*AP*TP*AP*GP*(C36)P*GP*CP*TP*AP*TP*C)-3')ProSAT+
1nfkPROTEIN (NUCLEAR FACTOR KAPPA-B (NF-KB))DNA (5'-D(*TP*GP*GP*GP*AP*AP*TP*TP*CP*CP*C)-3')ProSAT+
1parPROTEIN (ARC REPRESSOR)DNA (5'-D(*AP*AP*TP*GP*AP*TP*AP*GP*AP*AP*GP*CP*AP*CP*TP*CP*T P*AP*CP*TP*AP*T)- 3')ProSAT+
1pdnPROTEIN (PRD PAIRED)DNA (5'-D(*TP*TP*GP*TP*CP*AP*AP*CP*CP*GP*TP*GP*AP*CP*G)-3')ProSAT+
1puePROTEIN (TRANSCRIPTION FACTOR PU.1 (TF PU.1))DNA (5'-D(*TP*CP*CP*CP*AP*CP*TP*TP*CP*CP*CP*CP*TP*TP*TP*T)-3')ProSAT+
1pviPROTEIN (PVUII (E.C.3.1.21.4))DNA (5'-D(*TP*GP*AP*CP*CP*AP*GP*CP*TP*GP*GP*TP*C)-3')ProSAT+
1pyiPROTEIN (PYRIMIDINE PATHWAY REGULATOR 1)DNA (5'-D(*TP*CP*GP*GP*CP*AP*AP*TP*TP*GP*CP*CP*GP*A)-3')ProSAT+
1rvcPROTEIN (ECO RV (E.C.3.1.21.4))DNA (5'-D(*AP*TP*CP*TP*T)-3')ProSAT+
1srsPROTEIN (SERUM RESPONSE FACTOR (SRF))DNA (5'-D(*CP*CP*AP*TP*GP*GP*CP*CP*TP*AP*AP*TP*TP*AP*GP*GP*A P*AP*G)-3')ProSAT+
1tauPROTEIN (TAQ POLYMERASE)DNA (5'-D(*CP*GP*GP*AP*TP*CP*GP*C)-3')ProSAT+
1tc3PROTEIN (TC3 TRANSPOSASE)DNA (5'-D(*AP*GP*TP*TP*CP*TP*AP*TP*AP*GP*GP*AP*CP*CP*CP*CP*C P*CP*CP*T)-3')ProSAT+
1trrPROTEIN (TRP REPRESSOR)DNA (5'-D(*AP*GP*CP*GP*TP*AP*CP*TP*AP*GP*TP*AP*CP*GP*CP*T)-3')ProSAT+
1tsrPROTEIN (P53 TUMOR SUPPRESSOR)DNA (5'-D(*AP*TP*AP*AP*TP*TP*GP*GP*GP*CP*AP*AP*GP*TP*CP*TP*A P*GP*GP*AP*A)-3')ProSAT+
1uaaPROTEIN (ATP-DEPENDENT DNA HELICASE REP.)DNA (5'-D(*TP*TP*TP*TP*TP*TP*TP*TP*TP*TP*TP*TP*TP*TP*TP*T)-3')ProSAT+
1urnPROTEIN (U1A)RNA (5'-R(*AP*AP*UP*CP*CP*AP*UP*UP*GP*CP*AP*CP*UP*CP*CP*GP*G P*AP*UP*UP*U)-3')ProSAT+
1vasPROTEIN (T4 ENDONUCLEASE V (E.C.3.1.25.1))DNA (5'-D(*TP*AP*GP*CP*GP*CP*AP*AP*CP*GP*CP*GP*A)-3')ProSAT+
1volPROTEIN (TATA BINDING PROTEIN (TBP))DNA (5'-D(*CP*AP*GP*CP*CP*CP*TP*TP*TP*TP*AP*TP*AP*GP*CP*C)-3')ProSAT+
1ysaPROTEIN (GCN4)DNA (5'-D(*AP*AP*AP*CP*TP*GP*GP*AP*TP*GP*AP*GP*TP*CP*AP*TP*A P*GP*GP*A)-3')ProSAT+
1ytfPROTEIN (TRANSCRIPTION FACTOR IIA - TOA2 SUBUNIT)DNA (5'-D(*GP*TP*TP*TP*TP*AP*TP*AP*TP*AP*CP*AP*TP*AP*CP*A)-3')ProSAT+
1zdiPROTEIN (RNA BACTERIOPHAGE MS2 COAT PROTEIN)RNA (5'-R(*AP*CP*AP*UP*GP*AP*GP*GP*AP*UP*UP*AP*CP*CP*CP*AP*U P*GP*U)-3')ProSAT+
2dgcPROTEIN (GCN4)DNA (5'-D(*TP*GP*GP*AP*GP*AP*TP*GP*AP*CP*GP*TP*CP*AP*TP*CP*T P*CP*C)-3')ProSAT+
2drpPROTEIN (TRAMTRACK DNA-BINDING DOMAIN)DNA (5'-D(*TP*CP*GP*GP*AP*CP*GP*TP*TP*AP*TP*CP*CP*TP*TP*AP*T P*TP*A)-3')ProSAT+
2gliPROTEIN (FIVE-FINGER GLI)DNA (5'-D(*AP*CP*GP*TP*GP*GP*AP*CP*CP*AP*CP*CP*CP*AP*AP*GP*AP*CP*GP*AP*A)-3')ProSAT+

Changes / Known Issues

Issues

  • In case you use an ad blocker with your browser, the JSMol visualization of the protein might not be loaded (Error message "Network error"). In this case, disable your ad blocker or put the molsurfer on the exception list.
  • Uploading two files, both without chain id causes an error
  • Using two unrelated proteins causes an error

Changes

  • 2018 reimplementation with JSMol. No Java required any longer.
  • Adding the following features:
    • Also added the feature to display B-Factor and electrostatic potential information in one run.
    • Support to start using PDB identifier
    • Dynamically load description and chain information for PDB entries. Chain information for files
    • Initial release using Java applet and webmol.