RESUMO
We show that a nonspecific hydrophobic energy function can produce protein-like folding behavior of a three-dimensional protein model of 40 monomers in the cubic lattice when the native conformation is chosen judiciously. We confirm that monomer inside/outside segregation is a powerful criterion for the selection of appropriate structures, an idea that was recently proposed with basis on a general theoretical analysis and simulations of much simpler two-dimensional models.
Assuntos
Dobramento de Proteína , Proteínas/química , Simulação por Computador , Temperatura Alta , Modelos Moleculares , Modelos Estatísticos , Modelos Teóricos , Método de Monte Carlo , Conformação Proteica , Temperatura , Termodinâmica , ÁguaRESUMO
A number of simple silyl enol ethers and vinyl trifluoromethanesulfonates, a relatively new class of organic compounds capable of undergoing alkylation by a nucleophilic addition-elimination process, were evaluated in the P388 lymphocytic leukemia system. No activity (ILS = 8-22%) was observed in the simple vinyl derivatives. Some activity (ILS = 20-42%) was observed for a series of siloxy and sulfonate (CH3SO2 and CF3SO3) functionalized alpha-methylene lactone systems. The enhanced activity of the functionalized systems over the parent methylene lactone is ascribed to a possible irreversible alkylation by cellular nucleophiles via a nucleophilic addition-elimination process.