News, page updates and bug fixes
When we make changes to the model, fix bugs, or we just want to share something cool with everyone, you'll see it here. If you are going to present work with these models at a conference, or if you publish a paper, send us an email and we'll be happy to add it as an announcement.
Dec 2016 An updated version 1.07 of WHAM.jar is available on the tools page. If you use this tool, make sure you use the updated version as it fixes an issue that often prolongs the convergence time for parallel runs.
October 31st, 2016 Noel and Whitford used SMOG models to show how EF-Tu can reduce the free-energy barrier of tRNA accommodation on the ribosome. The results appeared today in Nature Communications.
August 1st, 2016 Nguyen and Whitford used SMOG models to identify appropriate single-molecule labeling sites for measuring tRNA hybrid-state formation in the ribosome. The manuscript appeared in J. Phys. Chem. B.
March 10th, 2016 Our paper describing SMOG 2 appeared today in PLOS Computational Biology.
February 3rd, 2016 Nguyen and Whitford used SMOG models to identify a new collective tilting motion in the ribosome. The results appeared today in Nature Communications.
July 31st, 2015 Ramirez-Sarmiento et al uses SMOG to show how interdomain contacts control native state switching of RfaH on a dual-funneled landscape. The results were reported in PLOS Comp Bio.
July 20th, 2015 SMOG 2 is now available! This is a downloadable version of the software, which has been designed to provide a robust platform for the flexible design of new SMOG models. Check out the SMOG 2 page here.
May 2015 A user forum for smog users is now available. This is for discussion/questions regarding structure-based models, as well as the SMOG and SMOG 2 software. To sign up, go to the forum page.
December 2014 Noel et al use SMOG models to identify optimal coordinates for describing the large-scale accommodation process in the ribosome. The results were reported in Biophysical Journal.
Aug 1st, 2014 Lin et al. use dual-basin SMOG models to present the first dynamical picture of the massive functional rearrangment of the influenza virus glycoprotein hemagglutinin. The results were reported in PNAS.
May 22nd-23rd, 2014 Many members of the SMOG team and others who use SMOG models presented work at the 1st Symposium on Current Topics in Molecular Biophysics at the University of São Paulo, Brazil.
July 19th, 2013 Beta version of the downloadable local version of the webtool is available. It is based on Perl5 and XML. While we believe you will already find it useful, it is still an experimental version and we appreciate feedback.
June 11th, 2013 10,000th PDB converted to gro/top SBM. Keep up the great science!
January 17th, 2013 Walther et al. use SMOG models to help identify the structure and self-assembly properties of the TatA translocation pore. The results were reported in Cell.
November 2012 Lammert et al. show that backbone distortions decide the folding mechanism of SH3 in the Calpha model. The article appeared in PLoS Comp Bio
September 30th, 2012 MDfit is now officially supported with Gromacs Version 4.5.5. A tutorial and the code is available here.
September 20th, 2012 Jamros et al. used SMOG models to characterize changes in the configurational distribution of Csk upon substrate binding. The results were published in PLoS Comp. Biol..
July 13th, 2012 Sulkowska et al. uses SBMs to explore the landscape of a designed trefoil knotted protein. The manuscript appeared in PNAS.
May 8th, 2012 Sutto and Camilloni used SBMs to study the engineered proteins GA98 and GB98, which provided insights into how protein folding motifs may evolve. The manuscript appeared in J. Chem. Phys..
April 2012 Wang et al. studied large-scale conformational rearrangements in Maltose Binding Protein. They used SBMs to built a triple-basin model to identify the extent to which induced-fit and population-shift mechanisms are used. The manuscript appeared in PLoS Computational Biology.
April 26th, 2012 Noel et al. characterizes the shadow map and shows how it is a general contact map definition for capturing the dynamics of biomolecular folding and function. The manuscript appeared in J. Phys. Chem. B.
April 12th, 2012 Noel et al. uses SBMs to more fully explore the competing folded conformations of three helix bundles found in explicit solvent REMD simulations. The manuscript appeared in J. Phys. Chem. B.
March, 2012 Gaye et al. used SBMs to study the effects of mutations in the protein TOP7. The results were published in EPL.
November 13th, 2011 Altman et al. used modified SBMs to characterize the properties of novel FRET dyes. The results were presented in Nature Methods.
November 12th, 2011 Lammert et al. used modified SBMs to investigate the detailed role of protein side-chain excluded volume during folding. The results were presented in Proteins: Structure, Function Bioinformatics.
November 11th, 2011 Whitford et al. used SBMs as the foundation for building atomic models from cryo-EM data for the ribosome. The results were reported in PNAS. The described atomic models can be found here.
May 27th, 2011 Ferreira et al. used SBMs to interpret SAXS measurements, which demonstrated that PKD2 proteins likely form oligomeric assemblies in solution. The results were published in PNAS.
January 24th, 2011 Nechushtai et al. combined SBMs with x-ray crystallography, protein-film voltammetry and CD measurements to reveal hidden modes of long-range communication in a Ferredoxin protein domain. The results were published in PNAS.
December 2nd, 2010 Ratje et al. used the all-atom SBM to build atomic models of the ribosome during translocation. The results were published in Nature and can be accessed here. A press release on this work is available from the HPC wire.
August 26th, 2010 Jamros et al. used the all-atom SBM to model the ensemble of configurations of Csk that best accounts for measured Small Angle X-ray Scattering data. The results appeared in the Journal of Biological Chemistry, and can be accessed here.
August 11th, 2010 Noel et al. used the all-atom SBM to investigate the folding of complex topologies, namely a trefoil knotted protein. The paper can be accessed here.
June 7th, 2010 Paper describing the web server was published online in Nucleic Acid Research 2010 Web Server Issue. It can be accessed here.
April 28th, 2010 Whitford et al. used these models, in addition to explicit-solvent simulations and single-molecule FRET experiments, to study aminoacyl-tRNA accommodation in the ribosome. The results were published in RNA and can be accessed here with related videos on youtube.
December 29th, 2009 Using this webtool, Schug et al. utilized a structure-based forcefield to assist in modeling protein complexes. The results were published in PNAS and can be accessed here.
December 28th, 2009 With the use of this webtool and model, Camilloni and Sutto published results on the folding of Lymphotactin in J. Chem. Phys. Check it out here.
January 21st, 2009 Our initial all-atom paper on RNA appears in Biophysical Journal.
January 20th, 2009 Calpha model for proteins added to the webtool and tutorial.
November, 2008 "Shadow" contact analysis webtool for monomeric, and oligomeric, protein/RNA/DNA systems was released.
October, 2008 All-atom structure-based webtool for proteins, RNA and DNA is released.
September 2nd, 2008 Our initial all-atom paper on proteins is published online in Proteins: Structure, Function Bioinformatics.
Version History:If we update the forcefield generation code, it will be documented here. The version history for the Shadow Contact Map can be found elsewhere. The most up-to-date stable version can always be accessed HERE. Since new versions occasionally have bug fixes, it is highly recommended that you only use the newest supported version.
1.2.3: March 13th, 2016: The back-end code has been cleaned up.
1.2.2: July 13th, 2014: Updates include:
- The CBS sugar residue is supported.
- Bug fix regarding the use of BMG and Shadow. Shadow treated a BMG type 6 bond (used to constrain the ion) as a chemical bond, thus discarding native BMG contacts at an intermediate stage of generating the SBM Hamiltonian. Shadow now ignores type 6 bonds and BMG contacts are now correct.
- SMOG models have now been integrated within the OPTIM computational framework for Discrete Path Sampling (DPS), as developed by the Wales group. The model is identical as that used for simulations, except for a switching function used in the calculation of non-native interactions. We are organizing documentation and tutorials for the use of DPS with SMOG models.
- All-atom model only: You now have the option to use longer timesteps. In the past, a timestep of 0.0005 was suggested to ensure minimal numerical noise. We have found that is the strength of all bonds is reduced by a factor of 2, and bond angles are increased in strength by a factor of 2, then you can use a timestep of 0.002 without altering the results.
- A bug was fixed with regards to dihedrals in the CA model. While the page lets you select an arbitrary strength of the dihedrals, a value of 1 was being used. Functionality is now restored.
1.2.1: November 1st, 2012: This included 1 bug fix regarding the addition of charges.
1.2: August 31st, 2012: Updates include:
- It is now possible to include some charges in your system (Only supported with the all-atom models). If you opt for charges, the only charges that will be included are on the following residue:atom pairs : ARG:NH1=+1, LYS:NZ=+1, BMG=+2, GLU:OE1=-1, ASP:OD1=-1, N-terminal N atoms=+1, OXT atoms=-1 and backbone P (RNA/DNA) atoms will be given -1. Be very careful with this option. There are a few subtle points (i.e. constants built into Gromacs) that you should be familiar with before using this option. In other words, the energy scale is not calibrated by default. Rather, the charges are placed on the molecule, and the scale of the energetic terms may need to be modified by the user through altering the value of the dielectric constant used in the simulation.
- Additional ligands are supported. A complete list of supported ligands is: SAM,AP5,ADP,ATP,AMP,GTP,GDP,GNP,FUA,B12
- N-terminal Acetyl groups (ACE) are now supported.
- 3-(BENZOYLAMINO)-L-ALANINE is now supported (DBZ).
1.1.1: January 14nd, 2012: Energy assignments are now calculated using double precision and the parameters in the top file are output with higher precision. In earlier versions, for molecular systems of 100,000+ atoms, there were small errors that could accumulate and lead to changes in energy assignments of ~1%. Now, double precision eliminates these rounding errors. For example, in a system with 154690 atoms, the total stabilizing energy is 154690.000018. All indicated energy ratios are also within 0.1 % of the requested value.
- Change in energy distribution NOW, by default, all (NA and protein) backbone dihedrals are the same strength and all ligand dihedrals are the same strength. Also, you can now specify the relative strength of each set of backbone dihedrals.
- You can opt to not shift the coordinates. In Gromacs v4.5.X, you can use grid neighbor searching without using periodic boundary conditions, in which case it is not necessary to place the system in a box.
- Due to a rounding issue (pdb precision 0.001 Å , and Gromacs files 0.01 Å precision), in previous versions it was possible to obtain a different Shadow contact map (~1% of the contacts are different) if you use a different spacing, or you shift coordinates. Now, the map is calculated for an unshifted system, and it uses 0.01 precision, with values taken from the submitted pdb file. If you were to provide the same structure twice, where the coordinates are shifted in one of them, then it is still possible to get a different contact map. For the same pdb file, the Shadow map generated with GenTopGro (V > 1.0.6) is now identical to that generated with Shadow.pl.
- Shadow now supports BMG atoms.
- ZN atoms are now supported. They interact through harmonic interactions, as is done for BMG atoms.
- In all versions of this tool, the default mass of all atoms is 1.0. Since mass does not influence thermodynamic properties, this is often not a concern. If you perform kinetic simulations that do not sample a known thermodynamic ensemble, then the masses can affect the kinetic properties. Now, the webtool allows you to select for heterogeneous masses. C, O, N atoms are given a mass of 1.0, BMG is 2.0, P is 2.5 and ZN is 5.45. It is straightforward to further modify the masses by editing the .top file.
- A minor bug resulted in contacts with the S atom of the MIA residue not being included in the rescaling of stacking contacts, when using a cut-off contact map. Bug fixed.
- You can now upload your pdb file in gzipped or b2zipped format.
- When using the shadow option, the webtool will reformat and renumber the pdb file. Now, upon successful generation of a forcefield, you will be given the modified pdb (NAME.pdb) and the submitted pdb (NAME.pdb.orig). Also, when using the Shadow option, the log file will have 2 sets of messages. The first round of messages corresponds to the processing of NAME.pdb.orig and the second round is for NAME.pdb.
- The SPLICE option is now supported with the Shadow Contact Map.
- Gaussian contact potentials are now supported. The webtool will generate topology files with Gaussian contacts, if selected. These topology files must be run with our modified version of Gromacs, which is available here.
- It is now possible to select a Shadow Contact Map (SCM) with specific parameters (i.e. sequence separation, distance criterion and shadow size).
- The definition of sequence separation, for the calculations of contact maps, has changed from earlier versions of the webtool. NOW, for two residues i and j, they must be separated by |i-j|>sequence separation value. Before, it was |i-j|>=sequence separation value. That is, 3, in version >=1.1, is equivalent to 4 in versions <1.1.
Note on V <= 1.0.6 : (posted June 12th, 2011) Our previous descriptions of the energetic distribution for combined protein-NA systems was incomplete. While the ratio of contact-to-dihedrals and the ratio between backbone-sidechain dihedrals are calculated as described, and the total stabilizing energy is assigned properly, the relative strength of protein dihedral angles and NA dihedrals was not specified. When calculating the strengths of each, the program would assign 1 unit of energy to each protein sidechain dihedral. Then, backbone dihedrals were given the specified ratio (as provided to the webtool). Next, NA backbone dihedrals were given 1 unit of energy and the NA sidechains were given the ratio value submitted to the page. Then, all dihedrals were uniformly rescaled, in order to satisfy the total stabilizing energy and contact-dihedral ratio requirements. The resulting forcefield had protein backbone dihedrals and NA sidechain dihedrals at the same strength. A more intuitive assignment is to make all backbone dihedrals the same strength. We are updating the code now, and a minor modification for mixed protein-NA systems will appear in V>1.0.6.
1.0.6: February 8th, 2011: The modified NA residue 2-methylthio-N6 isopentenyl adenosine is now supported (resname MIA). GTP is supported. You may also splice an RNA chain (to the O3' atom) and protein chain (C-terminal atom, such as in aminoacyl-tRNA) by adding the field "SPLICE" between the chains (this would be in place of "TER" line). SPLICE is not supported with shadow, but we are working on adding that capability. Bound MG2+ atoms are now supported. Use the residue name and atom name "BMG". All contacts with BMG atoms will be included as harmonic restraints of strength 1 (not supported with shadow).
1.0.5: January 4rd, 2011: Fusidic Acid (FUA) and GDP are now supported ligands.
1.0.4: December 29th, 2010: A variety of minor fixes in rigid dihedral assignments for SAM, DNA, PRO, TRP, HIS and TYR. Since these degrees of freedom were sufficiently restrained before, these fixes should not affect results obtained with the model. Additionally, unnecessary error messages associated with DNA have been removed.
1.0.3: December 25th, 2010: The contact to dihedral ratio was fixed for ligands. Now, the strength of the dihedrals and contacts is determined by counting the number of dihedrals and contacts for the protein/nucleic acid system, excluding the ligand. The strengths are then used for the ligand. So, if you prepare the same system with and without the ligand, the only difference in the .top file should be the terms for the ligand. This means the total contact to total dihedral energy is what you specify for the system, if you exclude the ligand. If you do the sums with the ligand, then it will likely not be exact. As an example, the strength of a given phi angle should be the same, whether or not you have the ligand present.
1.0.2: December 14th, 2010: The scale of contacts to dihedrals for RNA has been fixed.
1.0.1: October 19th, 2010: A version number now appears in the generated .gro and .top files.
December 2nd, 2010: Additional Warning messages were added.
The page now gives a file that lists all of the parameters that were used to produce the forcefield.
The default name of the "molecule" in the top file is now "Macromolecule". It was "Protein", but we changed it to avoid confusion. This will have no effect on the simulations.
<1: February 2010: Shadow gave a shadowing radius of 0.5 Å to all atoms connected by bonds, angles, or dihedrals. This definition has been changed to mean only those atoms specified under "[ bonds ]" and not the connections under "[ angles ]" and "[ dihedrals ]". This could noticeably change folding temperatures.
Resolved Technical Issues:
Resolved Technical Issues:
July 12th, 2016 The server was intermittently unavailable due to routine maintenance.
April 29th, 2016 The server was temporarily unavailable for a few hours today.
July 16th, 2014 Contact map options were inaccessible in v1.2.2. Options are re-enabled.
April 22st, 2014 The server was taken down for unexpected maintenance. Service was restored after a few hours.
September 10th-11th, 2012 During migration and upgrade to smog-server.org, there were intermittent interruptions in service. Thank you for your patience during this transition.
December 12th-13th, 2011 Due to a server update, there was a brief interruption of SMOG availability. If you tried to generate a model during this period, you would have received a fatal error, even if the pdb file was formatted properly.
November 4th, 2011 For V<=1.0.6, if two atoms are too close, then they were omitted from the 'exclusions' list, which results in a slightly larger repulsive interaction between these atoms. This only happened if two CA atoms are closer than 2 Å (in the CA model) or if two atoms are within 1.5 Å (AA model). This has been resolved for V>=1.1.
July 5th, 2011 For Versions <=1.0.6, if you were to supply a contact map and one of an atom in a contact is not supported by the smog webtool (possibly due to misnamed atom in the pdb file), a warning message was issued, but the webtool did not return a fatal error. While a fatal error was not reported, it was possible that the forcefield may contain errors due to this. For V >=1.1, this warning is now a fatal error.
January 10th, 2011 There were cases where Shadow was treating DNA like protein and excluding residue i from having contacts with neighboring residues i-3 < j < i+3. This behavior is undesirable since nearest neighbor stacking interactions are important. DNA no longer excludes neighboring DNA residues from having contacts. RNA was already handled correctly.
December 25th, 2010 The contact to dihedral ratio was being calculated for the whole system, including ligands. Now, the contact/dihedral ratio is maintained for the protein/na system, excluding the ligand. So, if you prepare the same system with and without the ligand, the only difference in the .top file will be the terms for the ligand.
December 14th, 2010 There was an issue with the scaling of contacts to dihedrals for RNA. It appears to have been introduced on October 19th, 2010. If you generated RNA forcefields in this period, then this ratio may not be exactly what you indicated on the interface. If this ratio is important for the particular system you are studying (in many cases the results are insensitive to this value), it would be worth double checking that the total contact energy and total dihedral energy are appropriately scaled. Proteins and DNA were unaffected. We also changed the code so that the ratio of energies is preserved, even if you have missing atoms. Before, if you had atoms missing in your system (such as OXT atoms), then this ratio was perturbed as well (for this reason, it was always stressed to check your files, especially the output files).
June 16th, 2010 System maintenance resulted in a temporary interruption in service.
May 20th-June 1st, 2010 There was a temporary issue with generating CA-models for proteins with multiple chains. Functionality has been restored.
May 19th, 2010 2 energetic misassignments were identified and fixed for RNA/DNA. The bond angle for atoms C3*-O3*-P(i+1) was assigned twice. A rigid dihedral angle about the C5-C6 bond in A and G was assigned twice. Both assignments were corrected.
September 29th, 2009 A bug was identified and fixed: When using a CA model and uploading your own contact file, incorrect values were used for the excluded volume. All other combinations of models and contacts were unaffected.
September 28th/29th, 2009 Temporary issue with contact map calculations resulted in all generated files using a cut-off contact map with all-atom representation. If you calculated a .top and .gro file on these two days, double check your files.
August 24th/25th, 2009 Web page intermittently unavailable due to unexpected server issues. Functionality restored.
August 10th, 2009 A precision issue was fixed. For shadow contact calculations, we now use precision of 0.01 Å for coordinates. For technical reasons, we still use 0.001 A precision for coordinates when calculating cut-off contact maps. This difference will be resolved soon.