SQM2.20: Semiempirical quantum-mechanical scoring function yields DFT-quality protein-ligand binding affinity predictions in minutes.

0582928 - ÚOCHB 2025 RIV US eng J - Článek v odborném periodiku
Pecina, Adam - Fanfrlík, Jindřich - Lepšík, Martin - Řezáč, Jan
SQM2.20: Semiempirical quantum-mechanical scoring function yields DFT-quality protein-ligand binding affinity predictions in minutes.
Nature Communications. Roč. 15, February (2024), č. článku 1127. E-ISSN 2041-1723
Výzkumná infrastruktura: e-INFRA CZ II - 90254
Institucionální podpora: RVO:61388963
Klíčová slova: NDDO approximations * free-energies * docking
Impakt faktor: 16.6, rok: 2022
Způsob publikování: Open access
https://doi.org/10.1038/s41467-024-45431-8

Accurate estimation of protein-ligand binding affinity is the cornerstone of computer-aided drug design. We present a universal physics-based scoring function, named SQM2.20, addressing key terms of binding free energy using semiempirical quantum-mechanical computational methods. SQM2.20 incorporates the latest methodological advances while remaining computationally efficient even for systems with thousands of atoms. To validate it rigorously, we have compiled and made available the PL-REX benchmark dataset consisting of high-resolution crystal structures and reliable experimental affinities for ten diverse protein targets. Comparative assessments demonstrate that SQM2.20 outperforms other scoring methods and reaches a level of accuracy similar to much more expensive DFT calculations. In the PL-REX dataset, it achieves excellent correlation with experimental data (average R2=0.69) and exhibits consistent performance across all targets. In contrast to DFT, SQM2.20 provides affinity predictions in minutes, making it suitable for practical applications in hit identification or lead optimization.
Trvalý link: https://hdl.handle.net/11104/0350971


Vědecká data: ZENODO