Graphene or MoS nanopores: pore adhesion and protein linearization.

Nanopores drilled in materials can electrophoretically drive charged biomolecules to enable their detection. Here, we explore and compare two-dimensional nanopores, graphene and MoS, in order to unravel their advantages and disadvantages with regard to protein detection. We tuned the protein translocation and its dynamics by the choice and concentration of the surrounding solvent.

Mechanism of activation and autophosphorylation of a histidine kinase.

Histidine kinases (HK) are one of the main prokaryotic signaling systems. Two structurally conserved catalytic domains inside the HK enable autokinase, phosphotransfer, and phosphatase activities. Here, we focus on a detailed mechanistic understanding of the functional cycle of the WalK HK by a multi-scale simulation approach, consisting of classical as well as hybrid QM/MM molecular dynamics simulation.

Extended-sampling QM/MM simulation of biochemical reactions involving P-N bonds.

The description of the phosphate group and its reactions with nitrogen species appears to be challenging using semi-empirical quantum chemical methods, and this holds for DFTB3 too. A new parameterization of DFTB3, consisting of a new P-N repulsive function, has been developed to improve its performance for reactions in which a P-N bond is replaced by a P-O bond or . Extended-sampling QM/MM simulations using the new parameterization of DFTB3 represent biochemical phosphorylation and hydrolysis reactions involving P-N bonds accurately.

Accurate Free Energies for Complex Condensed-Phase Reactions Using an Artificial Neural Network Corrected DFTB/MM Methodology.

Semiempirical methods like density functional tight-binding (DFTB) allow extensive phase space sampling, making it possible to generate free energy surfaces of complex reactions in condensed-phase environments. Such a high efficiency often comes at the cost of reduced accuracy, which may be improved by developing a specific reaction parametrization (SRP) for the particular molecular system. Thiol-disulfide exchange is a nucleophilic substitution reaction that occurs in a large class of proteins.