Assessment of the Binding Affinity of Covalent Inhibitors of Cruzain and Cathepsin L Using Relative Binding Free Energy
Yan Carvalho Magno, Luiz Fernando Barbosa, Maycon Vinicius Damasceno de Oliveira, Jerônimo Lameira, Carlos A. Montanari · 2026
Read Assessment of the Binding Affinity of Covalent Inhibitors of Cruzain and Cathepsin L Using Relative Binding Free Energy by Yan Carvalho Magno, Luiz Fernando Barbosa, Maycon Vinicius Damasceno de Oliveira, Jerônimo Lameira, Carlos A. Montanari (2026) in the Tower of Babel, a free online library of public-domain works preserved in clean, searchable text. No sign-up. The full text is served as a plain-text file at a predictable URL, where text is present: https://antarctic-labs.com/tower-of-babel/PMC13616992.txt.
Description
Yan Carvalho Magno and four colleagues test how tightly six nitrile-based inhibitors bind two cysteine proteases. The first is cruzain, the main protease of the parasite that causes Chagas disease. The second is human cathepsin L, a cancer drug target. Both enzymes share the same catalytic pairing, which lets one chemical family block either of them. The team measured binding strength in the laboratory and then modeled it on a computer.
Molecular dynamics simulations with thermodynamic integration, a method that computes binding energy differences step by step, reproduced the measured ranking of the six inhibitors closely. A structural difference in one pocket of the enzymes, the S2 subsite, explained why some compounds preferred one target over the other. The authors say the validated protocol can guide design of better inhibitors for Chagas disease and for cancer therapy.
Catalog record
| CREATOR | Yan Carvalho Magno, Luiz Fernando Barbosa, Maycon Vinicius Damasceno de Oliveira, Jerônimo Lameira, Carlos A. Montanari |
|---|---|
| YEAR | 2026 |
| COLLECTION | PAPERS |
| FORMAT | TXT |
| FILE SIZE | 36 KB |
| LICENSE | https://creativecommons.org/licenses/by/4.0 |
| RIGHTS | CC BY |
| SOURCE | Europe PMC |