De Novo Prediction of Binders
and Nonbinders for T4
Lysozyme by gREST Simulations
Posted on 2019-08-21 - 15:17
Molecular
recognition underpins all specific protein–ligand
interactions and is essential for biomolecular functions. The prediction
of canonical binding poses and distinguishing binders from nonbinders
are much sought after goals. Here, we apply the generalized replica
exchange with solute tempering method, gREST, combined with a flat-bottom
potential to evaluate binder and nonbinder interactions with a T4
lysozyme Leu99Ala mutant. The buried hydrophobic cavity and possibility
of coupled conformational changes in this protein make binding predictions
difficult. The present gREST simulations, enabling enhanced flexibilities
of the ligand and protein residues near the binding site, sample bindings
in multiple poses, and correct portrayal of X-ray structures. The
free-energy profiles of binders (benzene, ethylbenzene, and n-hexylbenzene) are distinct from those of nonbinders (phenol
and benzaldehyde). Bindings of the two larger molecules seem to be
associated with a structural change toward an excited conformation
of the protein, which agrees with experimental findings. The protocol
is generally applicable to various proteins having buried cavities
with limited access for ligands with different shapes, sizes, and
chemical properties.
CITE THIS COLLECTION
DataCite
3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
4OR
AAPG Bulletin
AAPS Open
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Niitsu, Ai; Re, Suyong; Oshima, Hiraku; Kamiya, Motoshi; Sugita, Yuji (2019). De Novo Prediction of Binders
and Nonbinders for T4
Lysozyme by gREST Simulations. ACS Publications. Collection. https://doi.org/10.1021/acs.jcim.9b00416
or
Select your citation style and then place your mouse over the citation text to select it.
SHARE
Usage metrics
Read the peer-reviewed publication
AUTHORS (5)
AN
Ai Niitsu
SR
Suyong Re
HO
Hiraku Oshima
MK
Motoshi Kamiya
YS
Yuji Sugita
KEYWORDS
replica exchangenonbinder interactionsbinding predictionsT 4 LysozymeDe Novo Predictionprotein residuescavitychemical propertiesgREST simulationsbinding sitefree-energy profilesgREST Simulations Molecular recognitioncanonical bindingX-ray structuresligandbiomolecular functionsT 4 lysozyme Leu 99Alasample bindings