The voltage-dependent anion channel (VDAC) mediates metabolite and ion flow across the outer mitochondrial membrane of all eukaryotic cells. The open channel passes millions of ATP molecules per second, while the closed state exhibits no detectable ATP flux. High-resolution structures of VDAC1 revealed a 19-stranded β-barrel with an α-helix partially occupying the central pore. To understand ATP permeation through VDAC, we solved the crystal structure of mouse VDAC1 (mVDAC1) in the presence of ATP, revealing a low-affinity binding site. Guided by these coordinates, we initiated hundreds of molecular dynamics (MD) simulations to construct a Markov State Model (MSM) of ATP permeation. These simulations indicate that ATP flows through VDAC using multiple pathways, consistent with our structural data and experimentally determined physiological rates.

The present study was designed to elaborate on the morphometry of the skull of non-descript goats in Mizoram state of India. The study was conducted on the skull of twelve (n=12) adult goats of either sex (n=6 males and n=6 females) collected from the local slaughterhouses. Altogether, forty-one different measurements were taken morphologically. In the present study, the cranial and facial bones were the major components of the skull with a total of thirty-two bones. There were three single and four paired cranial bones with a total of eleven bones. There were one single and the rest were paired facial bones with a total of twenty-one bones. The cranial bones were occipital, parietal, interparietal, sphenoid, ethmoid, frontal and temporal. The facial bones were maxilla, premaxilla (incisive), palatine, pterygoid, nasal, lacrimal, zygomatic (malar), vomer, turbinate, mandible and hyoid. The skull measurements showed that the skull of the goat was elongated and dolichocephalic as per the cephalic index (47.82±0.05). The length and width of the skull was 19.28±0.03 cm and 9.22±0.04 cm, respectively. There were two supraorbital foramina on both sides of the frontal bone. The prominent facial tuberosity lies dorsally to the third superior premolar tooth. Single infraorbital foramen was located dorsally to the junction of the first and second superior premolar teeth on maxilla bone. The orbits were round and complete and situated on a frontolateral oblique plane. It can be concluded that the findings of this study would assist the comparative studies with other domesticated animals in the future and would be applicable in clinical veterinary practice and even in zooarchaeology.

Electrostatic forces are one of the primary determinants of molecular interactions. They help guide the folding of proteins, increase the binding of one protein to another and facilitate protein-DNA and protein-ligand binding. A popular method for computing the electrostatic properties of biological systems is to numerically solve the Poisson-Boltzmann (PB) equation, and there are several easy-to-use software packages available that solve the PB equation for soluble proteins. Here we present a freely available program, called APBSmem, for carrying out these calculations in the presence of a membrane. The Adaptive Poisson-Boltzmann Solver (APBS) is used as a back-end for solving the PB equation, and a Java-based graphical user interface (GUI) coordinates a set of routines that introduce the influence of the membrane, determine its placement relative to the protein, and set the membrane potential. The software Jmol is embedded in the GUI to visualize the protein inserted in the membrane before the calculation and the electrostatic potential after completing the computation. We expect that the ease with which the GUI allows one to carry out these calculations will make this software a useful resource for experimenters and computational researchers alike. Three examples of membrane protein electrostatic calculations are carried out to illustrate how to use APBSmem and to highlight the different quantities of interest that can be calculated.

The voltage-dependent anion channel (VDAC) is the major pathway mediating the transfer of metabolites and ions across the mitochondrial outer membrane. Two hallmarks of the channel in the open state are high metabolite flux and anion selectivity, while the partially closed state blocks metabolites and is cation selective. Here we report the results from electrostatics calculations carried out on the recently determined high-resolution structure of murine VDAC1 (mVDAC1). Poisson-Boltzmann (PB) calculations show that the ion transfer free energy through the channel is favorable for anions, suggesting that mVDAC1 represents the open state. This claim is buttressed by Poisson-Nernst-Planck (PNP) calculations that predict a high single-channel conductance indicative of the open state and an anion selectivity of 1.75 – nearly a 2-fold selectivity for anions over cations. These calculations were repeated on mutant channels and gave selectivity changes in accord with experimental observations. We were then able to engineer an in silico mutant channel with three point mutations that converted mVDAC1 into a channel with a preference for cations. Finally, we investigated two proposals for how the channel gates between the open and closed state. Both models involve the movement of the N-terminal helix, but neither motion produced the observed voltage sensitivity, nor did either model result in a cation selective channel, which is observed experimentally. Thus, we were able to rule out certain models for channel gating, but the true motion has yet to be determined.

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studies on the skull of Indian Blackbuck (Antelope cervicapra). Int. J. Morphol., 33(3):868-876, 2015. SUMMARY:The phenotypic appearance of the head of animal species depends strongly on the shape of the skull. The morphometric studies of the skull show that variability in the shape and proportions of bones is influenced by genetic and environmental factors. The present study was carried out first time on the morphometrical characteristics on skull of Indian Blackbuck. Craniometric measurements for 48 different parts of the skulls of Indian blackbuck were made in this study. All investigated features were expressed as Mean±SE. The craniometric measurements and cephalic indices had been compared with ruminants. The mean lengths of the skulls were found to be 20.68±0.02 cm, with the width and cephalic index to the magnitude of 9.54±0.03 cm and 46.12±0.12 cm, respectively. The cranial length, width and height in blackbuck were 10.40±0.02 cm, 6.13±0.02 cm and 7.13±0.02 cm, respectively. The cranial index was 59.00±0.11. The mean facial length, facial width and facial index were 11.53±0.08 cm, 9.30±0.01 cm and 80.67±0.44 cm, respectively. The mean weight of the skull with mandible in blackbuck was 182.37±0.54.