March 2022: QuantumBio Product Updates

Welcome to the March 2022 announcement on our product updates! We have been working hard to bring you some much-requested features over the past year. Here, we describe the changes we’ve made to our software suite. Read along to learn about how these features can help accelerate and streamline your drug discovery and development research.

Overhauled molecular perception capabilities

What changed:
The entirety of the molecular perception process has been overhauled to increase the robustness of MovableType (MT) and molecular mechanics methods.

Why it matters:
To increase compatibility with 3rd party dockers and molecular modeling tools, Input-based perception allows users to verify and pass atom type information from other tools to DivCon and increase consistency within alternative preparation protocols.

MTScore

Improved model preparation

What changed:
We’ve added optimization methods when alternative binding modes are presented from 3rd party software (like MOE, GLIDE, and so on).

Why it matters:
In prior versions, MT was highly dependent upon the quality of the binding modes provided by the user. This means if the docking software or other tools generated poses that had bad clashes or other problems, they could negatively impact results. This version provides integrated methods for structure preparation which are invoked to improve predictions.

Greater support for bound target:ligand (holo) and unbound target (apo) ensembles in partition function calculations

What changed:
We’ve expanded the options available that allow the user to provide holo and apo conformer poses generated with molecular dynamics (or Monte Carlo) snapshots.

Why it matters:
The accuracy of the protein:ligand (ZPL) and protein (ZP) partition functions directly impact the ability of free energy methods to be predictive. Greater bound target:ligand and unbound target sampling lead to improved opportunities for greater predictability of the MT method—especially in cases when the target exhibits greater flexibility during binding.

Support for AMBERFF14SB and AMBERFF19SB in MovableType

What changed:
The GARF potential has been the standard pair potential used to calculate the ZP, ZPL, and ZL partition functions in MT since the beginning. In the last two years, we have added a second pair potential — based on AMBER functional potential. This version has this potential completely validated for use in MT (and in QM/MM) including several different standard versions (AMBERFF14SB & AMBERFF19SB).

Why it matters:
The accuracy of the pair potential is directly related to the accuracy of any underlying free energy method (like MT). So access to more pair potentials means more structures and targets which can be treated with this innovative method.

Integrated MOE support for MTScoreES

What changed:
EndState MTScore is now fully integrated with MOE for communication with either WebService or commandline when executed from the MOE (or MOE/batch) platform.

Why it matters:
As referenced in our recent publications, MOE is an often-used platform for structure-based drug discovery (SBDD) and for MTScore. The MOE plugin has been further updated and is now available for use.

BUSTER/DivCon

Improved XModeScore support for and integration with the BUSTER X-ray crystallographic platform

What changed:
Tautomer/protomer generation (which is used in XModeScore) is more robust when challenged with multiple ligand copies (chains). The tautomers/protomers are also more complete.

Why it matters:
Since not everyone has PHENIX, it is important that we cover additional crystallographic platforms. BUSTER is an extremely popular platform and we are excited to fully support it with qbbuster, BUSTER/DivCon, and XModeScore.

Tutorials

Updated tutorials for MovableType, BUSTER/DivCon, and PHENIX/DIvCon

What changed:
We’ve added three new tutorials to help our users navigate the software.

A lot has changed over the last year as MovableType and BUSTER/DivCon (including XModeScore) have matured. Additional options are now available to properly prepare input structures and generate alternative tautomer/protomer states and these options are now documented on the QuantumBio website.