Abstract
Abstract. Knowledge of free ligand conformational preferences
(energy minima) and conformational dynamics (rotational energy barriers) of
small molecules in solution can guide drug design hypotheses and help rank
ideas to bias syntheses towards more active compounds. Visualization of
conformational exchange dynamics around torsion angles, by replica exchange with solute tempering molecular dynamics (REST-MD), gives results in agreement with high-resolution 1H nuclear magnetic resonance (NMR) spectra and complements free ligand conformational analyses. Rotational energy barriers around individual
bonds are comparable between calculated and experimental values, making the
in-silico method relevant to ranking prospective design ideas in drug discovery programs, particularly across a series of analogs. Prioritizing
design ideas, based on calculations and analysis of measurements across a
series, efficiently guides rational discovery towards the “right molecules”
for effective medicines.
Reference38 articles.
1. ACD/NMR Workbook: version 2020.1.2, Advanced Chemistry Development, Inc.,
Toronto, ON, Canada, available at: http://www.acdlabs.com, last access: 10 June 2021.
2. Atilaw, Y., Poongavanam, V., Nilsson, C. S., Nguyen, D., Giese, A., Meibom,
D., Erdelyi, M., and Kihlberg, J.: Solution Conformations Shed Light on
PROTAC Cell Permeability, ACS Med. Chem. Lett., 12, 107–114, https://doi.org/10.1021/acsmedchemlett.0c00556, 2021.
3. Balazs, A. Y. S.: NMR free ligand conformations and atomic resolution dynamics, compound 1, Chemotion-Repository [data set], https://doi.org/10.14272/GRTREOMLNXYRCK-CRICUBBOSA-N.1, 2021a.
4. Balazs, A. Y. S.: NMR free ligand conformations and atomic resolution dynamics, compound 2, Chemotion-Repository [data set], https://doi.org/10.14272/WCXZZJFDRDQAHJ-WXTAPIANSA-N.1, 2021b.
5. Balazs, A. Y. S.: NMR free ligand conformations and atomic resolution dynamics, compound 3, Chemotion-Repository [data set], https://doi.org/10.14272/UZTVFIJYDQIRSV-MZNJEOGPSA-N.1, 2021c.
Cited by
5 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献