Abstract
Human lactate dehydrogenase-A (LDHA) is emerging as a promising anticancer target. Up to now, structure-based investigations for identifying inhibitors of this enzyme have not explicitly accounted for active site flexibility. In the present study, by combining replica exchange molecular dynamics with network and cluster analyses, we identified reliable LDHA conformations for structure-based ligand design. The selected conformations were challenged and validated by retrospective virtual screening simulations.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemistry*
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Catalytic Domain
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Cluster Analysis
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Crystallography, X-Ray
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Drug Design
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Enzyme Inhibitors / chemistry*
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Humans
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / chemistry
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L-Lactate Dehydrogenase / antagonists & inhibitors
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L-Lactate Dehydrogenase / chemistry*
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Lactate Dehydrogenase 5
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Ligands
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Molecular Dynamics Simulation*
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Protein Binding
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Protein Conformation
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ROC Curve
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User-Computer Interface*
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Isoenzymes
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Ligands
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L-Lactate Dehydrogenase
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Lactate Dehydrogenase 5