Recent applications of computational methods to allosteric drug discovery

Interest in exploiting allosteric sites for the development of new therapeutics has grown considerably over the last two decades. The chief driving force behind the interest in allostery for drug discovery stems from the fact that in comparison to orthosteric sites, allosteric sites are less conserv...

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Published inFrontiers in molecular biosciences Vol. 9; p. 1070328
Main Authors Govindaraj, Rajiv Gandhi, Thangapandian, Sundar, Schauperl, Michael, Denny, Rajiah Aldrin, Diller, David J
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 12.01.2023
Subjects
allostery
computational modeling
fragment-based screening
Molecular Biosciences
molecular dynamics
structure-based design
computational modeling
molecular dynamics
structure-based design
fragment-based screening
allostery
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Summary:Interest in exploiting allosteric sites for the development of new therapeutics has grown considerably over the last two decades. The chief driving force behind the interest in allostery for drug discovery stems from the fact that in comparison to orthosteric sites, allosteric sites are less conserved across a protein family, thereby offering greater opportunity for selectivity and ultimately tolerability. While there is significant overlap between structure-based drug design for orthosteric and allosteric sites, allosteric sites offer additional challenges mostly involving the need to better understand protein flexibility and its relationship to protein function. Here we examine the extent to which structure-based drug design is impacting allosteric drug design by highlighting several targets across a variety of target classes.
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These authors have contributed equally to this work and share first authorship
Lu Shaoyong, Shanghai Jiao Tong University, China
Edited by: Gennady Verkhivker, Chapman University, United States
Reviewed by: Peichen Pan, Zhejiang University, China
This article was submitted to Biological Modeling and Simulation, a section of the journal Frontiers in Molecular Biosciences
ISSN:2296-889X
2296-889X
DOI:10.3389/fmolb.2022.1070328