Sampling and energy evaluation challenges in ligand binding protein design
نویسندگان
چکیده
منابع مشابه
Sampling and energy evaluation challenges in ligand binding protein design
The steroid hormone 17α-hydroxylprogesterone (17-OHP) is a biomarker for congenital adrenal hyperplasia and hence there is considerable interest in development of sensors for this compound. We used computational protein design to generate protein models with binding sites for 17-OHP containing an extended, nonpolar, shape-complementary binding pocket for the four-ring core of the compound, and ...
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Free energy calculations are used to study how strongly potential drug molecules interact with their target receptors. The accuracy of these calculations depends on the accuracy of the molecular dynamics (MD) force field as well as proper sampling of the major conformations of each molecule. However, proper sampling of ligand conformations can be difficult when there are large barriers separati...
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Cells contain a multitude of different chemical reaction paths running simultaneously and quite independently next to each other. This amazing feat is enabled by molecular recognition, the ability of biomolecules to form stable and specific complexes with each other and with their substrates. A better understanding of this process, i.e. of the kinetics, structures and thermodynamic properties o...
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Although the importance of protein dynamics in protein function is generally recognized, the role of protein fluctuations in allosteric effects scarcely has been considered. To address this gap, the Kullback-Leibler divergence (Dx) between protein conformational distributions before and after ligand binding was proposed as a means of quantifying allosteric effects in proteins. Here, previous ap...
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The goal of structure-based drug design is to create a ligand which binds with high affinity to a protein target. An exciting prospect is the ability to carry out this design process computationally and thereby obtain a series of drug leads which are potent and which can be subsequently optimized for druglike properties. In an earlier paper, we presented the wormhole method [1] which, subject t...
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ژورنال
عنوان ژورنال: Protein Science
سال: 2017
ISSN: 0961-8368
DOI: 10.1002/pro.3317