Alivexis, Inc., a preclinical-stage computation-driven drug discovery company, announces that a research article entitled “ModBind_dG: a simulation-based absolute predictor of free energy of binding based on population reweighting” by William Sinko et al. has been published in Proceedings of the National Academy of Sciences of the United States of America (PNAS).

This article describes the methodology, validation, and application of the company’s ground-breaking simulation technology, which enables rapid, accurate prediction of ligand binding affinity as absolute binding free energy at speeds up to thousands of times faster than existing simulation-based methods without any reference compound data. Alivexis developed ModBind_dG™ from fundamental theory and refined the method for accurate, large-scale application, enabling the company to push the boundaries of computation-driven drug discovery. ModBind_dG™ has been used extensively to accelerate Alivexis’ drug discovery programs and has supported pharma collaborations and the advancement of multiple clinical candidate molecules in the company’s pipeline.Image: “ModBind_dG: A novel free energy method for the prediction of ligand affinity against drug targets.  Accelerated bound and unbound simulations rapidly yield the key data for the calculation of binding potency.  Essential mathematical equations are shown.”

Publication information
Title: ModBind_dG: a simulation-based absolute predictor of free energy of binding based on population reweighting
Authors: William Sinko, Blake Mertz, Yoh Terada and S. Roy Kimura (Alivexis, Inc.)
Journal: Proceedings of the National Academy of Sciences of the United States of America (PNAS)
DOI: 10.1073/pnas.2513285123
Publication date: June 15^th, 2026, ET (online)

【CEO S. Roy Kimura’s Comments】
“We are excited to announce the publication of our research article on ModBind_dG™, the latest version of core technology platform at Alivexis. This publication is an important milestone because it demonstrates the scientific foundation of a technology that has already contributed to our internal pipeline and pharma collaborations. By enabling faster and accurate absolute prediction of binding free energy, ModBind_dG™ strengthens our ability to discovery high-quality small molecule candidates and create value through strategic partnerships.”

【Head of Computational Chemistry, William Sinko’s Comments】
“ModBind_dG™ predicts ligand binding affinity by estimating absolute binding free energy through a rigorous simulation-based methodology. Under accelerated sampling conditions we simulate the physical unbinding of molecules and determine the ratio of populations between bound and unbound states, which directly gives the absolute free energy of binding.  This theoretical framework, together with optimizations of our simulation protocol, opens the door to accurate free energy predictions with orders-of-magnitude lower computational time. We believe this approach can support compound evaluation across early drug discovery, from finding the first hit molecule to lead-optimization.”

Alivexis announces publication of a research article on its ground-breaking ModBind_dG™ simulation technology(PDF)