The covalent complex of Jo-In results from a long-lived, non-covalent intermediate state with near-native structure.

Covalent protein complexes have been used to assemble enzymes in large scaffolds for biotechnology purposes. Although the catalytic mechanism of the covalent linking of such proteins is well known, the recognition and overall structural mechanisms driving the association are far less understood but could help further functional engineering of these complexes. Here, we study the Jo-In complex by NMR spectroscopy and molecular modelling.

In silico study of amphiphilic nanotubes based on cyclic peptides in polar and non-polar solvent.

The stability of cyclic peptide assemblies (CPs) forming a macromolecular nanotube structure was investigated in solvents of different polarity using computational methods. The stability and structure of the complexes were studied using traditional molecular dynamics (MD). Energy of dissociation was estimated from steered MD in combination with umbrella sampling simulations.

AlaScan: A Graphical User Interface for Alanine Scanning Free-Energy Calculations.

Computation of the free-energy changes that underlie molecular recognition and association has gained significant importance due to its considerable potential in drug discovery. The massive increase of computational power in recent years substantiates the application of more accurate theoretical methods for the calculation of binding free energies. The impact of such advances is the application of parent approaches, like computational alanine scanning, to investigate in silico the effect of amino-acid replacement in protein-ligand and protein-protein complexes, or probe the thermostability of individual proteins.

Theoretical studies on the transport mechanism of 5-fluorouracil through cyclic peptide based nanotubes.

Cyclic peptide nanotubes (CPNTs) formed by the self-assembly of cyclic peptides (CPs) with an even number of alternate l/d amino acids are typically used in the field of the transport of ions and drug molecules across the lipid bilayer. This study investigates the transport mechanism of the antitumor drug molecule, 5-fluorouracil (5FU), through the CPNT using classical and steered molecular dynamics simulations combined with umbrella sampling. During the transport of 5FU through the CPNT, 5FU is partially desolvated because the lumen of the CPNT is too small to allow for water molecules solvating it.

Structure and stability of cyclic peptide based nanotubes: a molecular dynamics study of the influence of amino acid composition.

The stability of self-assembling cyclic peptides (CPs) is attained by the intermolecular backbone-backbone hydrogen bonding (H-bonding) interactions. In addition to these H-bonding interactions, the self-assembled CPs are further stabilized by various intermolecular side chain-side chain interactions. This study investigates the role of amino acids on the structure and stability of self-assembled CPs using classical molecular dynamics (MD) simulations and molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) method.

3D-QSAR studies on the inhibitory activity of trimethoprim analogues against Escherichia coli dihydrofolate reductase.

Three-dimensional quantitative structure activity relationship (3D-QSAR) study has been carried out on the Escherichia coli DHFR inhibitors 2,4-diamino-5-(substituted-benzyl)pyrimidine derivatives to understand the structural features responsible for the improved potency. To construct highly predictive 3D-QSAR models, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods were used. The predicted models show statistically significant cross-validated and non-cross-validated correlation coefficient of r2 CV and r2 nCV, respectively.

3D-QSAR and docking studies on the HEPT derivatives of HIV-1 reverse transcriptase.

Three-dimensional Quantitative Structure Activity Relationship (3D-QSAR) has been derived for a set of HEPT derivatives of HIV-1 reverse transcriptase (RT) using Comparative Molecular Field Analysis (CoMFA). The CoMFA models have been developed using two different alignment procedures such as common substructure and bioactive conformation. The CoMFA model I is derived from a common substructure procedure that includes steric and electrostatic fields with the cross-validated q(2) and the non-cross-validated r(2) value of 0.

Redesigning of anti-c-Met single chain Fv antibody for the cytoplasmic folding and its structural analysis.

Typically, single chain Fv antibodies are unable to fold properly under a reducing cytoplasm because of the reduction of disulfide bonds. The inability to fold limits both the production of the functional scFvs and their targeting against antigens, which are generally executed in a reducing cytoplasm. In this study, the target scFv CDR was grafted with stable human consensus framework sequences, which enabled the generation of a foldable scFv in a reducing cytoplasm of Escherichia coli.

Bonding, aromaticity, and structure of trigonal dianion metal clusters.

Various isomers of the trigonal dianion metal clusters, X(3)(2-), X = Be, Mg, Ca, and their mono- and disodium complexes are optimized at the B3LYP/6-311+G(d) level. Different conceptual density functional theory based reactivity descriptors as well as the induced magnetic field values are calculated to understand the stability and aromaticity of these systems. Possibility of bond stretch isomerism is explored.