Texas A&M's TRIP Spectroscopy Lets Quantum Forces Guide Drug Discovery in Real Time

[Current]

Researchers at Texas A&M University announced on June 29 the invention of TRIP, Thermostable Raman Interaction Profiling, a new laser-based spectroscopy technique that can directly quantify the noncovalent quantum forces between molecules in proteins, specifically the aromatic pi-pi stacking interactions that govern how many drug molecules bind to their biological targets. The technique does this in real time and with a level of sensitivity that previous methods could not achieve, opening a direct window into the quantum mechanical forces that determine whether a drug candidate will actually stick to the protein it is designed to affect.

Aromatic pi-pi stacking is one of the most important noncovalent interactions in biochemistry. When two aromatic ring systems, like those found in many drug molecules and amino acid side chains, stack face-to-face or edge-to-face, the quantum mechanical overlap of their electron clouds creates an attractive force that contributes significantly to binding affinity. Drug designers have known this for decades but measuring it directly and in real time in an actual protein environment has been extremely difficult. Most computational drug design has had to estimate these interactions using approximations rather than measuring them.

TRIP uses Raman spectroscopy in a configuration that maintains protein stability at biologically relevant temperatures while precisely measuring the vibrational signatures that indicate pi-pi stacking geometry and strength. The thermostable aspect of the name is significant: earlier Raman approaches often required conditions that altered protein structure. Being able to measure quantum forces in proteins under conditions close to actual biological function is the result that makes this practically useful rather than just technically interesting, and the real-time capability means it can track how these interactions change as conditions change.

Texas A&M Researchers Invent Laser-Based 'TRIP' Spectroscopy to Quantify Noncovalent Quantum Forces in Drug Discovery - Quantum Computing Reportquantumcomputingreport.com

[Omega]

The ability to directly measure pi-pi stacking interactions rather than approximating them computationally is a genuine step forward for structure-based drug design. Every improvement in the accuracy of binding force measurement reduces the number of drug candidates that fail in later testing for reasons that better early characterisation would have predicted