Search results for "Metallo enzyme"

showing 2 items of 2 documents

Computing Metal-Binding Proteins for Therapeutic Benefit

2021

Over one third of biomolecules rely on metal ions to exert their cellular functions. Metal ions can play a structural role by stabilizing the structure of biomolecules, a functional role by promoting a wide variety of biochemical reactions, and a regulatory role by acting as messengers upon binding to proteins regulating cellular metal-homeostasis. These diverse roles in biology ascribe critical implications to metal-binding proteins in the onset of many diseases. Hence, it is of utmost importance to exhaustively unlock the different mechanistic facets of metal-binding proteins and to harness this knowledge to rationally devise novel therapeutic strategies to prevent or cure pathological st…

Functional roleModels MolecularMetalloenzymesCellular functionsMetallo enzymeMolecular ConformationComputational biologyMolecular Dynamics01 natural sciencesBiochemistryQM/MMDockingMetals HeavyDrug DiscoveryBiochemical reactionsMetal transportersGeneral Pharmacology Toxicology and PharmaceuticsPharmacology010405 organic chemistryOrganic ChemistryComputational BiologyMetal binding proteins0104 chemical sciences010404 medicinal & biomolecular chemistryDocking (molecular)Settore CHIM/03 - Chimica Generale E InorganicaMolecular MedicineCarrier Proteins
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Can multiscale simulations unravel the function of metallo-enzymes to improve knowledge-based drug discovery?

2019

Metallo-enzymes are a large class of biomolecules promoting specialized chemical reactions. Quantum-classical quantum mechanics/molecular mechanics molecular dynamics, describing the metal site at quantum mechanics level, while accounting for the rest of system at molecular mechanics level, has an accessible time-scale limited by its computational cost. Hence, it must be integrated with classical molecular dynamics and enhanced sampling simulations to disentangle the functions of metallo-enzymes. In this review, we provide an overview of these computational methods and their capabilities. In particular, we will focus on some systems such as CYP19A1 a Fe-dependent enzyme involved in estroge…

Models MolecularSpliceosomeQM/MM molecular dynamicsProtein ConformationComputer scienceMetallo enzymeComputational biology01 natural sciencesMolecular mechanicsribozymeStructure-Activity Relationship03 medical and health sciencesMolecular dynamicsMM molecular dynamicsAromataseCatalytic DomainDrug Discoverysteroid synthesisCYP19A1RNA CatalyticDensity Functional Theory030304 developmental biologyQMPharmacologychemistry.chemical_classificationDNA processing enzymes0303 health sciencesMetallo-proteinsbiologyDrug discoveryBiomoleculeRibozymeDNABiosynthetic PathwaysEnzymes0104 chemical sciences010404 medicinal & biomolecular chemistrychemistrySettore CHIM/03 - Chimica Generale E InorganicaMetalsbiology.proteinRNAThermodynamicsMolecular MedicinespliceosomeFunction (biology)Protein BindingFuture Medicinal Chemistry
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