Uma perspectiva computacional sobre catálise enzimática

Arantes, Guilherme Menegon

doi:10.1590/s0100-40422008000200034

Cited by 5 publications

(4 citation statements)

References 37 publications

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“…Outra limitação desses campos de força é não permitir que ocorra a quebra ou formação de novas ligações, impedindo que mecanismos de catálise enzimática sejam estudados. 185 Para contornar esta limitação podem-se usar simulações híbridas com mecânica quântica e clássica (QM/MM).…”

Section: Simulações De Dinâmica Molecular Aplicadas Na Busca Virtualunclassified

Busca Virtual De Compostos Bioativos: Conceitos E Aplicações

Piccirillo¹,

Amaral²

2018

Quim. Nova

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VIRTUAL SCREENING OF BIOACTIVE COMPOUNDS: CONCEPTS AND APLICATIONS. The search and use of bioactive compounds for different applications have been investigated, since ancient time. Virtual screening (VS) has emerged as alternative methodological approach to the Combinatory Chemistry and High-Throughput Screening (HTS) in identifying novel drug candidates. In VS, only compounds that are selected applying different computational tools to huge virtual libraries of compounds are further tested in vitro. However, the effective use of VS model applications have some challenges such as the inherent complexity of the ligand-receptor interactions as well as by other factors such as ligand and receptor multiple conformations and also ligand metabolic stabilities and toxicities. Altogether these difficulties are hardly overcome using only one computational tool. Therefore, in the literature, it has been suggested to apply a sequence of different filters, such as filters that select compounds through similarity, pharmacophore and docking. In this review, we describe the advantages, limitations and examples of recent successful applications of some of these filters, including drug-like properties, structural properties, 2D similarity, pharmacophore, shape and docking filters. Moreover, we present the main steps involved in the preparation of virtual libraries of compounds that can be used in the VS.

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Section: Simulações De Dinâmica Molecular Aplicadas Na Busca Virtualunclassified

Busca Virtual De Compostos Bioativos: Conceitos E Aplicações

Piccirillo¹,

Amaral²

2018

Quim. Nova

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“…Several strategies can be employed by enzymes to catalyze reactions. , We have shown in the previous section that Fcc 3 may protonate the fumarate C4 carboxylate by His504 in a relay type of general-acid catalysis (Figure b). We also discarded covalent catalysis in the form of intermediates covalently bound to the flavin ring because reactions that form adducts with FAD are too energetic (Figure ).…”

Section: Resultsmentioning

confidence: 99%

Dissecting Reaction Mechanisms and Catalytic Contributions in Flavoprotein Fumarate Reductases

Curtolo

Arantes

2023

J. Chem. Inf. Model.

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The interconversion between fumarate and succinate is fundamental to the energy metabolism of nearly all organisms. This redox reaction is catalyzed by a large family of enzymes, fumarate reductases and succinate dehydrogenases, using hydride and proton transfers from a flavin cofactor and a conserved Arg side-chain. These flavoenzymes also have substantial biomedical and biotechnological importance. Therefore, a detailed understanding of their catalytic mechanisms is valuable. Here, calibrated electronic structure calculations in a cluster model of the active site of the Fcc3 fumarate reductase were employed to investigate various reaction pathways and possible intermediates in the enzymatic environment and to dissect interactions that contribute to catalysis of fumarate reduction. Carbanion, covalent adduct, carbocation, and radical intermediates were examined. Significantly lower barriers were obtained for mechanisms via carbanion intermediates, with similar activation energies for hydride and proton transfers. Interestingly, the carbanion bound to the active site is best described as an enolate. Hydride transfer is stabilized by a preorganized charge dipole in the active site and by the restriction of the C1–C2 bond in a twisted conformation of the otherwise planar fumarate dianion. But, protonation of a fumarate carboxylate and quantum tunneling effects are not critical for catalysis of the hydride transfer. Calculations also suggest that the driving force for enzyme turnover is provided by regeneration of the catalytic Arg, either coupled with flavin reduction and decomposition of a proposed transient state or directly from the solvent. The detailed mechanistic description of enzymatic reduction of fumarate provided here clarifies previous contradictory views and provides new insights into catalysis by essential flavoenzyme reductases and dehydrogenases.

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“…Logo, o aumento da velocidade por efeitos entrópicos é frequentemente considerado um importante mecanismo catalítico (ARANTES, 2008).…”

Section: Uso De Anticorpos Com Efeitos Entrópicosunclassified

<b>Anticorpos catalíticos e suas aplicações em biotecnologia</b> - doi: 10.5102/ucs.v10i2.1583

Macedo¹,

Queiroz²

2012

Univ. Ci. Saúde

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Características peculiares como a alta especifi cidade dos anticorpos e o efi ciente poder catalítico das enzimas têm despertado um grande interesse em grupos de pesquisa científi ca no que diz respeito a possíveis reações obtidas pela junção dessas duas moléculas. O objetivo deste trabalho é realizar uma revisão bibliográfi ca sobre a constituição e obtenção dos anticorpos catalíticos e suas potenciais aplicações em biotecnologia. A tecnologia de anticorpos catalíticos já demonstrou a capacidade dessas moléculas em mediar diversas reações e vem abrindo relevantes possibilidades de aplicações em áreas industriais, agrícolas e biotecnológicas. Aliada à prática médica, os anticorpos catalíticos são grande promessa para fi ns diagnósticos e terapêuticos, desde a destruição de células cancerígenas e microrganismos, até a elaboração de vacinas catalíticas para as mais diversas fi nalidades, como a desintoxicação defi nitiva de pacientes com dependência química.

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Uma perspectiva computacional sobre catálise enzimática

Cited by 5 publications

References 37 publications

Busca Virtual De Compostos Bioativos: Conceitos E Aplicações

Busca Virtual De Compostos Bioativos: Conceitos E Aplicações

Dissecting Reaction Mechanisms and Catalytic Contributions in Flavoprotein Fumarate Reductases

<b>Anticorpos catalíticos e suas aplicações em biotecnologia</b> - doi: 10.5102/ucs.v10i2.1583

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