STATE COLLEGE, PENNSYLVANIA [February 09, 2021] – QuantumBio Inc. published results on the impact of QuantumBio’s X-ray refinement toolkit on binding affinity prediction and how crystallography and computer-aided drug design (CADD) can be used—synergistically—to improve our understanding of structure and function. The article is currently available under Open Access and will be published in a special issue of the Journal of Computer-AidedMolecular Design (JCAMD). It demonstrates how industrial and academic pharmaceutical researchers can create a “feedback loop” between computational chemistry and structural biology to improve their understanding of protein:ligand chemistry in the hopes of building better drugs—faster and cheaper.
Previously, QuantumBio showed that its Phenix/DivCon and BUSTER/DivCon (QM/MM) X-ray refinement tools yield superior-quality protein:ligand structures compared to conventional refinement. In the present JCAMD paper, the researchers used the Phenix/DivCon (QM/MM) refinement plugin to characterize 55 X-ray structures involving five different kinase targets from the Community Structure-Activity Resource (CSAR). They assessed the impact of QM/MM X-ray refined structures on the ability to predict (e.g., rank order) protein:ligand binding affinities using industry-standard score functions. Notably, they demonstrate that improved QM/MM crystal structures generate significantly more accurate binding affinity predictions, revealing that these new QM/MM X-ray models are not only better representations of protein:ligand structures, but they are more chemically descriptive of the key interactions critical to the drug discovery effort. Furthermore, predicted binding affinity outliers remaining even after QM/MM refinement were used to indicate additional structural issues and “fed back” to the X-ray crystallography effort for further analysis and correction. Finally, QuantumBio’s patented XModeScore method was used to successfully determine the correct tautomer/protomer states and “flip states” of ligands andactive sites of interest, bolstering the accuracy of binding affinity predictions.
“By utilizing our tools, we have demonstrated that improved structures yield improved predictions along with a better understanding of the critical interactions enabling protein:ligand binding. In fact, we have shown that these robust tools fuel a computational chemistry-structural biology feedback loop, creating more effective avenues for structure-based drug discovery,” Dr. Lance Westerhoff, President of QuantumBio.
The results suggest that researchers can greatly enhance score function predictability and overall structure-based drug design performance through better, chemically accurate protein:ligand structures. This synergistic approach is being replicated within industrial and academic pharmaceutical laboratories. Learn more about the software by reading the full publication titled “The critical role of QM/MMX-ray refinement and accurate tautomer/protomer determination in structure-based drug design,” and reach out to our team at sales@quantumbioinc.com to request an evaluation.
About QuantumBio Inc.
QuantumBio Inc. is a software and services company that provides innovative technical solutions to pharmaceutical, life sciences, and biotechnology companies and academic scientists to enhance the drug discovery process by improving their understanding of biochemical structure and function. QuantumBio offers a powerful suite of products built on cutting-edge science that utilizes the highest levels of theory to achieve high accuracy, performance, and versatility.