Publication

Duocarmycins binding to DNA explored by molecular simulation

Ursula Röthlisberger, Paolo Carloni
2005
Conference Papers

Abstract

Duocarmycins are a potent class of antitumor agents. Their activity arises by their covalent binding to adenine nucleobases of DNA. We use classical mol. dynamics and hybrid (QM/MM) Car-Parrinello mol. dynamics simulations to study non-covalent and covalent binding of three duocarmycins with different reactivities, namely DSA, DSI and NBOC-DSA. Reactions in water are explored for NBOC-DSA with adenine and simple model reactants. Our calcns. suggest that: (i) Non-covalent drug binding does not significantly perturb the DNA structure. (ii) The exptl. obsd. DNA catalytic power might be due, at least in part, to a polarization of the biomol. scaffold over the drugs. Instead, our calcns. do not support the "shape induced activation" mechanism, in which the conformational properties of the drug play a pivotal role for catalysis (5). (iii) The chem. nature of the drug influences the structure of the drug-DNA adduct, thus affecting the reactivity of the initial complex. (iv) The functional groups of the drugs affect the intrinsic reactivity of the compd. [on SciFinder (R)]

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https://infoscience.epfl.ch/entities/publication/3faddee9-d399-4e00-ae4e-0aa3df84f320

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Ursula Röthlisberger, Paolo Carloni
2005
Conference Papers

Abstract

Official source

https://infoscience.epfl.ch/entities/publication/3faddee9-d399-4e00-ae4e-0aa3df84f320

About this result

Related concepts (32)

Non-covalent interaction

In chemistry, a non-covalent interaction differs from a covalent bond in that it does not involve the sharing of electrons, but rather involves more dispersed variations of electromagnetic interactions between molecules or within a molecule. The chemical energy released in the formation of non-covalent interactions is typically on the order of 1–5 kcal/mol (1000–5000 calories per 6.02 molecules). Non-covalent interactions can be classified into different categories, such as electrostatic, π-effects, van der Waals forces, and hydrophobic effects.

Drug

A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhalation, injection, smoking, ingestion, absorption via a patch on the skin, suppository, or dissolution under the tongue. In pharmacology, a drug is a chemical substance, typically of known structure, which, when administered to a living organism, produces a biological effect.

Binding site

In biochemistry and molecular biology, a binding site is a region on a macromolecule such as a protein that binds to another molecule with specificity. The binding partner of the macromolecule is often referred to as a ligand. Ligands may include other proteins (resulting in a protein-protein interaction), enzyme substrates, second messengers, hormones, or allosteric modulators. The binding event is often, but not always, accompanied by a conformational change that alters the protein's function.

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