Computational design of a protein crystal

Protein crystals have catalytic and materials applications and are central to efforts in structural biology and therapeutic development. Designing predetermined crystal structures can be subtle given the complexity of proteins and the noncovalent interactions that govern crystallization. De novo protein design provides an approach to engineer highly complex nanoscale molecular structures, and often the positions of atoms can be programmed with sub-Å precision. Herein, a computational approach is presented for the design of proteins that self-assemble in three dimensions to yield macroscopic crystals. A three-helix coiled-coil protein is designed de novo to form a polar, layered, three-dimensional crystal having the P6 space group, which has a “honeycomb-like” structure and hexameric channels that span the crystal. The approach involves: (i) creating an ensemble of crystalline structures consistent with the targeted symmetry; (ii) characterizing this ensemble to identify “designable” structures from minima in the sequence-structure energy landscape and designing sequences for these structures; (iii) experimentally characterizing candidate proteins. A 2.1 Å resolution X-ray crystal structure of one such designed protein exhibits sub-Å agreement [backbone root mean square deviation (rmsd)] with the computational model of the crystal. This approach to crystal design has potential applications to the de novo design of nanostructured materials and to the modification of natural proteins to facilitate X-ray crystallographic analysis.     

Simulated screening of flavonoids as probable anti-Helicobacter pylori drug

Helicobacter pylori is a major causative factor during severe gastrointestinal disorders which leads to gastric ulcer in turn gastric cancer. Discovery of drugs to control H. pyloriis a difficult task in view of drug resistance developed by the bacterium against continuous exposure to modern drugs. The virtual screening is an important tool which cut down the man power, costand time by aiming at more toward target lead identification. It involves an in silico approach which enables to predict favorable protein–ligand interactions with reasonable accuracy and speed. In this perspective, virtual screening of a set of 51 flavonoid molecules for the inhibition of a key metabolic enzyme peptide deformylase (PDF) was carried out. Nobiletin, silibin, and vitexicarpin have revealed the lowest binding energy of ?10.65, ?11.46, and ?10.37 kJ mol^?1, respectively, which indicates high binding affinity with target protein and identified as anti-H. pylori molecules.     

Structure and mechanism of proton transport through the transmembrane tetrameric M2 protein bundle of the influenza A virus

The M2 proton channel from influenza A virus is an essential protein that mediates transport of protons across the viral envelope. This protein has a single transmembrane helix, which tetramerizes into the active channel. At the heart of the conduction mechanism is the exchange of protons between the His37 imidazole moieties of M2 and waters confined to the M2 bundle interior. Protons are conducted as the total charge of the four His37 side chains passes through 2⁺ and 3⁺ with a pK_a near 6. A 1.65 Å resolution X-ray structure of the transmembrane protein (residues 25–46), crystallized at pH 6.5, reveals a pore that is lined by alternating layers of sidechains and well-ordered water clusters, which offer a pathway for proton conduction. The His37 residues form a box-like structure, bounded on either side by water clusters with well-ordered oxygen atoms at close distance. The conformation of the protein, which is intermediate between structures previously solved at higher and lower pH, suggests a mechanism by which conformational changes might facilitate asymmetric diffusion through the channel in the presence of a proton gradient. Moreover, protons diffusing through the channel need not be localized to a single His37 imidazole, but instead may be delocalized over the entire His-box and associated water clusters. Thus, the new crystal structure provides a possible unification of the discrete site versus continuum conduction models.     

Antibacterial and molecular docking studies of entagenic acid, a bioactive principle from seed kernel of Entada pursaetha DC

In vitro antibacterial activity of a phytoconstituent, entagenic acid isolated from the seed kernel of Entada pursaetha DC was screened against both gram negative and gram positive bacteria. The entagenic acid showed the high antibacterial activity against B. cereus and B. subtilis with minimal inhibitory concentration of 200?μg?ml^?1 and possesses better glucosamine-6-phosphate synthase inhibition in molecular docking studies with minimum docking energy ?9.22?kJ?mol^?1, binding energy ?9.28?kJ?mol^?1 and inhibition constant 1.57e?007. The inhibition constant of streptomycin was 3.86e?005.