DivCon Plugin
The Engine that Powers accurate X-ray Crystallography Refinement.
With QuantumBio, you can improve structure-aided drug design using a top-tier protein crystallographic refinement toolkit: DivCon integrated with your platform of choice—validated against numerous protein-ligand structures and the quantum mechanics refinement protocol.
- Quickly determine the appropriate conformation of the ligand and generate ligand conformations more consistent with X-ray data.
- Ensure the correct model and eliminate bias associated with conventional methods—our tools are based on quantum mechanics, generating restraints in “real-time” and requiring less a priori knowledge of the final structure.
- Easily integrate the software into your workflow with our command line accessibility and optional MOE GUI plugin.
- Use your platform of choice—whether you are using PHENIX or BUSTER, you’ll get the results you need.
- Optimize your methods and get your questions answered quickly with our responsive team—We are here to help!
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Choose your Platform
| Phenix/DivCon Helpful information for the PHENIX users |
Buster/DivCon Helpful information for the BUSTER users |
Rigorous software and your partner in refinement
Overcome the limitation of fixed empirical stereochemistry restraints in conventional X-ray refinement by using our solution: rigorous, integrated, and automatic mixed-quantum mechanics/molecular mechanics (QM/MM) treatment of protein:ligand complexes, DNA, and RNA.
Do you have a particular PDBid that you would like to see treated at this level of theory? Email the PDBid to info@quantumbioinc.com and we’ll be happy to send you the results so you can see what these tools can do for you!
PDB Details:
PDB ID: 1MRL
PDB Title: Crystal Structure of Streptogramin A Acetyltransferase with Dalfopristin
Deposition year: 2002
Experimental Method: X-RAY DIFFRACTION
Resolution: 2.8 Å
Space Group: P21 21 21
Unit Cell:
a=82.91α=90.00
b=90.90β=90.00
c=104.53γ=90.00
| Original PDB | QM-Refinement | |
|---|---|---|
| R-work | 0.272 | 0.232 |
| R-free | 0.304 | 0.310 |
Ligand Details:
Ligand ID: DOL (Chain A)
Ligand Formula: C34 H50 N4 O9 S
Ligand Name: 5-(2-DIETHYLAMINO-ETHANESULFONYL)-21-HYDROXY-10-ISOPROPYL-11,19-DIMETHYL-9,26-DIOXA-3,15,28-TRIAZA-TRICYCLO[23.2.1.00,255]OCTACOSA-1(27),12,17,19,25(28)-PENTAENE-2,8,14,23-TETRAONE
| Original PDB | QM-Refinement | |
|---|---|---|
| Ligand Strain Energy (PM6 Kcal/Mole) | 667.17 | 57.78 |
PDB Details:
PDB ID: 2CJU
PDB Title: Crystal Structure Of The Tepc15-Vk45.1 Anti-2-Phenyl-5-Oxazolone NQ16-113.8 SCFV in Complex with Phoxgaba
Deposition year: 2006
Experimental Method: X-RAY DIFFRACTION
Resolution: 2.5 Å
Space Group: I 21 21 21
Unit Cell:
a=51.97α=90.00
b=74.19β=90.00
c=134.18γ=90.00
| Original PDB | QM-Refinement | |
|---|---|---|
| R-work | 0.241 | 0.216 |
| R-free | 0.291 | 0.300 |
Ligand Details:
Ligand ID: PHX
Ligand Formula: C14 H12 N2 O4
Ligand Name: 4-{[(Z)-(5-OXO-2-PHENYL-1,3-OXAZOL-4(5H)-YLIDENE)METHYL]AMINO}BUTANOIC ACID
| Original PDB | QM-Refinement | |
|---|---|---|
| Ligand Strain Energy (PM6 Kcal/Mole) | 557.58 | 16.85 |
PDB Details:
PDB ID: 2JK7
PDB Title: XIAP BIR3 Bound to a SMAC Mimetic
Deposition year: 2008
Experimental Method: X-RAY DIFFRACTION
Resolution: 2.82 Å
Space Group: P 65 2 2
Unit Cell:
a=115.76α=90.00
b=115.76β=90.00
c=61.79γ=120.00
| Original PDB | QM-Refinement | |
|---|---|---|
| R-work | 0.229 | 0.214 |
| R-free | 0.276 | 0.263 |
Ligand Details:
Ligand ID: BI6
Ligand Formula: C36 H34 N4 O3 S
Ligand Name: (3S,6S,7Z,10AS)-N-(DIPHENYLMETHYL)-6-{[(2S)-2
-(METHYLIDENEAMINO)BUTANOYL]AMINO}-5-OXO-1,2,3,5,6,9,10,10
A-OCTAHYDROPYRROLO[1,2-A]AZOCINE-3-CARBOXAMIDE
| Original PDB | QM-Refinement | |
|---|---|---|
| Ligand Strain Energy (PM6 Kcal/Mole) | 260.03 | 35.46 |
Quickly propel your protein crystallography projects forward. At QuantumBio, we are constantly improving our platform and we are a dedicated collaborator. Our iterative approach delivers software that facilitates better workflows and methods—and most importantly better structures and predictions.
If you do not see results comparable to those provided, we want to hear from you so we can support you through the process. Contact Us today and we’ll schedule a “virtual visit” to discuss your goals and your chosen protocol.
It’s Finally Here: X-Ray Crystallography + Computer-Aided Drug Design
A computational chemistry (CADD) ↔ structural biology (X-ray crystallography) “feedback loop”— changing the game in protein:ligand crystallography and structure-based drug design for industrial and academic pharmaceutical researchers.
Enhance Protein Crystallography Refinement
Protein crystallography plays a critical role in structure-aided drug design, but conventional crystallographic tools often have difficulty accurately capturing the unusual chemistry and structure involving ligands, cofactors, and metals, along with their effects on the active site of a promising target.
This problem comes from the reliance on stereochemical restraints. These restraints are fairly well defined for standard amino acids, however for ligands and cofactors, they must be predetermined through “atom typing” and provided in a library or dictionary file—the creation of which is a time-consuming, error-prone process.
Furthermore, conventional methods do not account for the critical non-bonded interactions required to fully understand protein:ligand binding (e.g. hydrogen bonds, electrostatics, van der Waals, etc.).
We have replaced these fixed empirical stereochemistry restraints with a more rigorous quantum mechanical (QM) treatment of the complex—performed in situ (capturing the interactions between protein and ligand) and almost in real-time. By integrating QuantumBio’s linear-scaling, semi-empirical QM toolkit with the popular crystallographic packages PHENIX and BUSTER, the refinement utilizes QM and QM/MM gradients generated at each refinement cycle.
This “real-time restraint generation” requires less a priori knowledge of the final structure then conventional methods and is more attuned to the chemical influences of the active site on the ligand (and vise versa).
With Phenix/DivCon and Buster/DivCon, you’ll be able to
- Significantly improve ligand geometries in cases where conventional refinement has failed or where correct library creation has been problematic.
- Capture exotic chemistry associated with the ligand and/or any cofactors in the active site.
- Improve ligand strain energy determination.
CONTACT US LICENSE THE SOFTWARE
Frequently Asked Questions
Learn more about the DivCon plugin by reading through the full list of FAQs.
When should I employ quantum mechanics during the refinement? Should I use QM from the beginning or should I use it after I’m pretty sure of the structure?
The answer to this question will vary from problem to problem, but as a general rule, we recommend as early as possible.
One of the biggest benefits of the method is that it requires fewer a priori assumptions vs conventional methods. Conventional assumptions (e.g. stereochemical restraints) can quickly become biases. Granted, you need to know enough to make fairly accurate protonation predictions, but even with this requirement, Phenix/DivCon or BUSTER/DivCon can help.
If the starting geometry is in really bad shape, employ the macro_cycle_to_skip=1 command line option that will use the standard stereochemical restraints for a single, initial macrocycle in order to minimize the structure prior to QM refinement.
Does the DivCon plugin support multiple QM regions?
Yes. Simply use the qblib_region_selection= command line argument and request multiple regions. DivCon will automatically determine whether the regions overlap (according to the core/buffer size settings), and how to divide the system among the various processors requested. See the tutorial for more information.
How complete are the functions? Can it really account for electrostatics, hydrogen bonding, polarization and other quantum effects?
Yes!
Classical or molecular mechanics (MM) has its strengths, but in many cases, these force fields are playing “catch up” to quantum methods. Semiempirical quantum mechanics is able to capture these influences very well even for the relatively fast calculations that are employed during the DivCon refinement.
Granted, to get a more complete picture of dispersion and hydrogen bonding, higher level ab initio and DFT methods are required; however, these calculations are also much, much more expensive than semiempirical QM methods. For this reason, we believe that we have struck the proper balance between speed and accuracy.
Ultimately, compared with stereochemical restraint methods utilized in conventional refinement, the higher level methods found in DivCon are far superior.
Guidelines: X-ray Refinement
Learn the key considerations when performing QM-based refinement.
Phenix/DivCon and Buster/DivCon Manuals
Get installation instructions, configuration options, tutorials, and case studies.
Case Study: Where’s the Proton?
Learn how accurate crystallographic refinement using qm-methods can inform this often difficult choice.