R. A. Pearlstein

Improving the preclinical and clinical success rates of LMW drugs depends on radical revisions to the status quo scientific foundations of medicinal chemistry: a case study on COVID Mpro inhibition

This paper argues for a theoretical shift in medicinal chemistry to improve LMW drug success rates by applying Biodynamics to model cellular function and drug action in non-linear dynamic systems.

Toward a first principles understanding of the activation and deactivation mechanisms of class A G-protein coupled receptors and voltage-gated cation channels

This paper applies a multi-scale theory to analyze activation and deactivation mechanisms of GPCRs and VGCCs, proposing solvation dynamics as the driving force behind conformational changes.

Solvation dynamics-powered structure and function of multi-molecular cellular systems exemplified by non-equilibrium cereblon-degrader-CK1α ternary complex formation

The paper examines how solvation dynamics power structural and functional dynamics in multi-molecular complexes, exemplified by cereblon-degrader-CK1α interactions.

General structure-free energy relationships of hERG blocker binding under native cellular conditions

The paper analyzes hERG blocker binding using solvation field principles, showing correlations between solvation costs and blocker potency and safety.

Toward in vivo-relevant hERG safety assessment and mitigation strategies based on relationships between non-equilibrium blocker binding, three-dimensional channel-blocker interactions, dynamic occupancy, dynamic exposure, and cellular arrhythmia

This paper develops a two-step model of hERG blocker binding and proposes an improved safety assessment strategy incorporating dynamic occupancy, exposure, and disease factors.