Cytochrome P450 peroxygenases use hydrogen peroxide to hydroxylate long-chain fatty acids by bypassing the use of O 2 and a redox partner. Among the peroxygenases, P450 OleT uniquely performs decarboxylation of fatty acids and production of terminal olefins. This route taken by P450 OleT is intriguing, and its importance is augmented by the practical importance of olefin production. As such, this mechanistic choice merits elucidation. To address this puzzle, we use hybrid QM/ MM calculations and MD simulations for the OleT enzyme as well as for the structurally analogous enzyme, P450 BSβ . The study of P450 OleT reveals that the protonated His85 in the wild-type P450 OleT plays a crucial role in steering decarboxylation activity by stabilizing the corresponding hydroxoiron(IV) intermediate (Cpd II). In contrast, for P450 BSβ in which Q85 replaces H85, the respective Cpd II species is unstable and it reacts readily with the substrate radical by rebound, producing hydroxylation products. As shown, this single-site difference creates in P450 OleT a local electric field (LEF), which is significantly higher than that in P450 BSβ . In turn, these LEF differences are responsible for the different stabilities of the respective Cpd II/radical intermediates and hence for different functions of the two enzymes. P450 BSβ uses the common rebound mechanism and leads to hydroxylation, whereas P450 OleT proceeds via decarboxylation and generates terminal olefins. Olefin production projects the power of a single residue to alter the LEF and the enzyme's function.

The current theoretical perception of enzymatic activity is highly reliant on the determination of activation energy of the reactions which is often calculated using a computational demanding quantum mechanical calculation....

Applications of photochemistry are becoming very popular in modern‐day life due to its operational simplicity, environmentally friendly and economically sustainable nature in comparison to its thermochemistry. In particular photoinduced radical polymerisation (PRP) reaction is finding more biological applications and especially in the areas of dental restoration process, tissue engineering and artificial bone generation. Type‐II photoinitiator and co‐initiator promoted PRP turned out to be a cost effective protocol, and herein we report the design and synthesis of a new efficient co‐initiator for PRP reaction via barrierless sequential conjugate addition reaction. Experimental mechanistic observations were further complemented by computational data. Time for newly synthesised 1,2‐benzenedithiol (DTH) based co‐initiator promoted polymerisation of diurethane dimethacrylate (UDMA, 70%) and triethylene glycol dimethacrylate (TEGDMA, 30%) in presence of 450 nm LED (15 W) under the aerobic conditions was 38 seconds. High glass transition temperature, improved mechanical strength (860 BHN) and longer in‐depth polymerisation (3 cm) was observed.

Cytochrome P450 peroxygenases use hydrogen peroxide to hydroxylate long-chain fatty acids by bypassing the use of O 2 and a redox partner. Among the peroxygenases, P450 OleT uniquely performs decarboxylation of fatty acids and production of terminal olefins. This root taken by P450 OleT is intriguing, and its importance is augmented by the practical importance of olefin production. As such, this mechanistic choice merits elucidation. To address this puzzle we use hybrid QM/MM calculations and MD simulations for the OleT enzyme as well as for the structurally analogous enzyme, P450 BSβ . The study of P450 OleT reveals that the protonated His85 in the wild-type P450 OleT , plays a crucial role in steering decarboxylation activity by stabilizing the corresponding hydroxoiron(IV) intermediate (Cpd II). In contrast, for P450 BSβ in which Q85 replaces H85, the respective Cpd II species is unstable and it reacts readily with the substrate radical by rebound, producing hydroxylation products. As we show, this single-site difference creates in P450 OleT a local electric field (LEF), which is significantly higher than that in P450 BSβ . In turn, these LEF differences are responsible for the different stabilities of the respective Cpd II/radical intermediates, and hence for different functions of the two enzymes. P450 BSβ uses the common rebound mechanism and leads to hydroxylation, whereas P450 OleT proceeds via decarboxylation and generates terminal olefins. Olefin production projects the power of a single residue to alter the LEF and the enzyme’s function!

Alkylating agents possess the biggest threat to the genomic integrity of cell by damaging DNA bases through regular alkylation. Such damages are repaired by several automated machinery inside cell. O6-alkylguanine-DNA alkyltransferase (AGT) is such an enzyme which performs the direct repair of an alkylated guanine base by transferring the alkyl group to a Cysteine residue. In the present study using extensive MD simulations and hybrid QM/MM calculations, we have investigated the key interactions between the DNA lesion and the hAGT enzyme and elucidated the mechanisms of the demethylation of the guanine base. Our simulation shows that the DNA lesion is electrostatically stabilized by the enzyme and the Arg135 of hAGT enzyme provides the main driving force to flip the damaged base into the enzyme. The QM/MM calculations show demethylation of damaged base as a three step in thermodynamically feasible and irreversible manner. Our calculations show that the final products forms via Tyr114 in a facile way in contrast to the previously proposed Lys-mediated route.