Protein–ligand (un)binding kinetics as a new paradigm for drug discovery at the crossroad between experiments and modelling
| العنوان: | Protein–ligand (un)binding kinetics as a new paradigm for drug discovery at the crossroad between experiments and modelling |
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| المؤلفون: | Mattia Bernetti, Andrea Cavalli, Luca Mollica |
| المساهمون: | Bernetti, M., Cavalli, A., Mollica, L |
| المصدر: | MedChemComm. 8:534-550 |
| بيانات النشر: | Royal Society of Chemistry (RSC), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Pharmacology, Drug, Chemistry, Drug discovery, Nucleic acid structure determination, media_common.quotation_subject, Organic Chemistry, Rational design, Pharmaceutical Science, Binding process, Computational biology, Bioinformatics, Biochemistry, Receptor–ligand kinetics, 03 medical and health sciences, 030104 developmental biology, Molecular level, hemic and lymphatic diseases, Drug Discovery, Molecular Medicine, media_common, Protein ligand |
| الوصف: | In the last three decades, protein and nucleic acid structure determination and comprehension of the mechanisms, leading to their physiological and pathological functions, have become a cornerstone of biomedical sciences. A deep understanding of the principles governing the fates of cells and tissue at the molecular level has been gained over the years, offering a solid basis for the rational design of drugs aimed at the pharmacological treatment of numerous diseases. Historically, affinity indicators (i.e. Kd and IC50/EC50) have been assumed to be valid indicators of the in vivo efficacy of a drug. However, recent studies pointed out that the kinetics of the drug-receptor binding process could be as important or even more important than affinity in determining the drug efficacy. This eventually led to a growing interest in the characterisation and prediction of the rate constants of protein-ligand association and dissociation. For instance, a drug with a longer residence time can kinetically select a given receptor over another, even if the affinity for both receptors is comparable, thus increasing its therapeutic index. Therefore, understanding the molecular features underlying binding and unbinding processes is of central interest towards the rational control of drug binding kinetics. In this review, we report the theoretical framework behind protein-ligand association and highlight the latest advances in the experimental and computational approaches exploited to investigate the binding kinetics. |
| وصف الملف: | STAMPA |
| تدمد: | 2040-2511 2040-2503 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5c292ba01cf0a9b6c61509e0d39feaa7 https://doi.org/10.1039/c6md00581k |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....5c292ba01cf0a9b6c61509e0d39feaa7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20402511 20402503 |
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