JCIM Publication Explores the Impact of MD on MoveableType 

Journal of Chemical Information and Modeling Publication Explores the Impact of MD and MC Enhanced Sampling on MoveableType 

November 10, 2022: State College, PA, USA: A new publication evaluates QuantumBio’s MoveableType (MT) method as a fast free energy-based virtual screening tool when coupled with enhanced sampling methods – such as molecular dynamics (MD) and Monte Carlo (MC).  The Journal of Chemical Information and Modeling paper (co-authored by Wenlang Liu, Zhenhao Liu, Hao Liu, Lance M. Westerhoff, and Zheng Zheng) illustrates the prediction capability and computational efficiency of the MT method when using more thorough protein-ligand conformational sampling protocols. The result is a game-changer for the drug discovery toolkit – empowering life sciences researchers with additional receptor:ligand sampling progression options to optimize computational cost vs. predictability and solve even the most complex use-cases with MT.  

Successful structure-based drug discovery (SBDD) campaigns hinge on the availability of computational methods which accurately predict binding affinity between a target and potential drug compounds. Conventional free energy methods are extremely computationally expensive, error prone, and at times difficult to interpret – especially when they rely on relative binding affinity prediction. In contrast, QuantumBio’s MoveableType method has proven (in a 2020 JCIM study) to be highly accurate for absolute binding affinity prediction across a wide range of target systems at significantly less computational cost vs. conventional methods. 

In the previous work, the MT method was coupled with docking which resulted in acceptable predictive capability at a very reasonable computational cost (minutes per ligand) for a wide range of target classes. In the new paper, Dr. Zheng Zheng, Professor of Computational Chemistry, and his Wuhan University of Technology research group, demonstrate that MovableType, when coupled with enhanced sampling techniques such as molecular dynamics and Consecutive Histograms Monte Carlo (CHMC), is able to expand the applicability of MT to additional target:ligand cases beyond those relevant with the use of docking alone.  

“We’re excited by the results we’ve observed when MovableType is paired with molecular dynamics (i.e. Amber conventional MD protocol) and Monte Carlo sampling methods (i.e. CHMC protocol) for absolute protein:ligand binding affinity prediction,” said Dr. Zheng. “While MT (paired with docking) has shown itself to be very accurate for most protein:ligand structures, there are times when additional sampling is required. MD and CHMC coupled with MT are able to ‘rescue’ these cases.”

With the immediate availability of QuantumBio’s MoveableType molecular dynamics tool (MTMD), researchers can now apply MT to more SBDD projects with target (apo) and target:ligand (holo) sampling progression options to customize the optimal balance of computational expense vs. predictability for each campaign. Users can opt to use fast docking first and determine if it provides the level of predictability required for their drug discovery project. They can use cross-docking or multi-target conformer docking to explore alternative rotamer states and further improve binding affinity predictions. And now with this most recent work, they can pair MT with their preferred dynamics platform (e.g. AMBER, NAMD, GROMACS, etc.), spend a little more computational time to increase sampling, and obtain results that are more predictive than with just docking.

“Since we launched MovableType in the last two years, we have explored numerous cases with our clients, and the method has brought immense value to our customers,” said Dr. Westerhoff, President and General Manager, QuantumBio. “MD and CHMC expand the applicability of MT to additional use cases.”

MTMD – whether the molecular dynamics or Monte Carlo simulations are performed on your local cluster or in the cloud – is available now from QuantumBio for your drug discovery campaigns. Please contact QuantumBio for more information, or schedule a time to meet via Zoom, WebEx or on-site.

About QuantumBio Inc.

QuantumBio Inc is a software and services company that provides innovative technical solutions to the life sciences. QuantumBio Inc offers a powerful suite of products built on cutting-edge science that utilizes the highest levels of theory available to achieve high accuracy, performance, and versatility. QuantumBio’s tools leverage the precision of quantum mechanical approaches to aid pharmaceutical, biotech, and academic scientists to improve their understanding of biochemical structure and function while enhancing the drug discovery process.