Determination of Alkali and Halide Monovalent Ion Parameters for Use in Explicitly Solvated Biomolecular Simulations

Alkali (Li+, Na+, K+, Rb+, and Cs+) and halide (F−, Cl−, Br−, and I−) ions play an important role in many biological phenomena, roles that range from stabilization of biomolecular structure, to influence on biomolecular dynamics, to key physiological influence on homeostasis and signaling. To properly model ionic interaction and stability in atomistic simulations of biomolecular structure, dynamics, folding, catalysis, and function, an accurate model or representation of the monovalent ions is critically necessary. A good model needs to simultaneously reproduce many properties of ions, including their structure, dynamics, solvation, and moreover both the interactions of these ions with each other in the crystal and in solution and the interactions of ions with other molecules. At present, the best force fields for biomolecules employ a simple additive, nonpolarizable, and pairwise potential for atomic interaction. In this work, we describe our efforts to build better models of the monovalent ions within the pairwise Coulombic and 6-12 Lennard-Jones framework, where the models are tuned to balance crystal and solution properties in Ewald simulations with specific choices of well-known water models. Although it has been clearly demonstrated that truly accurate treatments of ions will require inclusion of nonadditivity and polarizability (particularly with the anions) and ultimately even a quantum mechanical treatment, our goal was to simply push the limits of the additive treatments to see if a balanced model could be created. The applied methodology is general and can be extended to other ions and to polarizable force-field models. Our starting point centered on observations from long simulations of biomolecules in salt solution with the AMBER force fields where salt crystals formed well below their solubility limit. The likely cause of the artifact in the AMBER parameters relates to the naive mixing of the Smith and Dang chloride parameters with AMBER-adapted Åqvist cation parameters. To provide a more appropriate balance, we reoptimized the parameters of the Lennard-Jones potential for the ions and specific choices of water models. To validate and optimize the parameters, we calculated hydration free energies of the solvated ions and also lattice energies (LE) and lattice constants (LC) of alkali halide salt crystals. This is the first effort that systematically scans across the Lennard-Jones space (well depth and radius) while balancing ion properties like LE and LC across all pair combinations of the alkali ions and halide ions. The optimization across the entire monovalent series avoids systematic deviations. The ion parameters developed, optimized, and characterized were targeted for use with some of the most commonly used rigid and nonpolarizable water models, specifically TIP3P, TIP4PEW, and SPC/E. In addition to well reproducing the solution and crystal properties, the new ion parameters well reproduce binding energies of the ions to water and the radii of the first hydration shells

Divalent Metal Ions Tune the Self-Splicing Reaction of the Yeast Mitochondrial Group II Intron Sc.ai5γ

Group II introns are large ribozymes, consisting of six functionally distinct domains that assemble in the presence of Mg2+ to the active structure catalyzing a variety of reactions. The first step of intron splicing is well characterized by a Michaelis–Menten-type cleavage reaction using a two-piece group II intron: the substrate RNA, the 5′-exon covalently linked to domains 1, 2, and 3, is cleaved upon addition of domain 5 acting as a catalyst. Here we investigate the effect of Ca2+, Mn2+, Ni2+, Zn2+, Cd2+, Pb2+, and [Co(NH3)6]3+ on the first step of splicing of the Saccharomyces cerevisiae mitochondrial group II intron Sc.ai5γ. We find that this group II intron is very sensitive to the presence of divalent metal ions other than Mg2+. For example, the presence of only 5% Ca2+ relative to Mg2+ results in a decrease in the maximal turnover rate k cat by 50%. Ca2+ thereby has a twofold effect: this metal ion interferes initially with folding, but then also competes directly with Mg2+ in the folded state, the latter being indicative of at least one specific Ca2+ binding pocket interfering directly with catalysis. Similar results are obtained with Mn2+, Cd2+, and [Co(NH3)6]3+. Ni2+ is a much more powerful inhibitor and the presence of either Zn2+ or Pb2+ leads to rapid degradation of the RNA. These results show a surprising sensitivity of such a large multidomain RNA on trace amounts of cations other than Mg2+ and raises the question of biological relevance at least in the case of Ca2+

Optimal selection of dental implant for different bone conditions based on the mechanical response

Bone quality varies from one patient to another extensively; also, Young’s modulus may deviate up to 40% of normal bone quality, which results into alteration of bone stiffness immensely. The prime goal of this study is to design the optimum dental implant considering the mechanical response at bone implant interfaces for a patient with specific bone quality. Method. 3D model of mandible and natural molar tooth were prepared from CT scan data while, dental implants were modelled using different diameter, length and porosity and FE analysis was carried out. Based on the variation in bone density, five different bone qualities were considered. First, failure analysis of implants, under maximum biting force of 250N had been performed; next, the implants, those survived were selected for observing the mechanical response at bone implant interfaces under common chewing load of 120N. Result. Maximum Von Mises stress did not surpass the yield strength of the implant material (TiAl4V). However, factor of safety of 1.5 was considered and all but two dental implants survived the design stress or allowable stress. Under 120N load, distribution of Von Mises stress and strain at the bone-implant interface corresponding to the rest of the implants for five bone conditions were obtained and enlisted. Conclusion. Implants, exhibiting interface strain within 1500-3000 microstrain range show the best bone remodelling and osseointegration. So, implant models, having this range of interface strains were selected corresponding to the particular bone quality. A set of optimum dental implants for each of the bone qualities were predicted

Exploration of urease-mediated biomineralization for defluoridation by Proteus columbae MLN9 with an emphasis on its genomic characterization

Fluoride (F-) contamination of groundwater is a silent killer of human health that has now become a global problem. In the present study, we sought to isolate fluoride-resistant, urease producing bacteria from F- contaminated groundwater to evaluate their potential F- biomineralization. Strain MLN9, isolated from the fluoride-contaminated village of Madhabpur in Birbhum, could resist up to 5600 mg L−1 F- concentration. Taxonomic classification of strain MLN9 based on whole genome sequence identified it as Proteus columbae MLN9. Strain MLN9 showed 88.9% of maximum F- removal efficiency at pH 8.0, 1.0 g L−1 CaCl2, and 10.0 g L−1 urea concentration. Scanning electron micrographs showed dense and porous biological crystal precipitates surrounding the surface of the bacterial cells, and the adherence of F- to the cell surface was confirmed by the energy dispersion spectrum. Moreover, the X-ray diffraction pattern showed that the F- precipitates on the cell surface were biological crystals of Ca5(PO4)3F and CaF2. Genomic analysis of strain MLN9 revealed the presence of crcB gene homologs possibly encoding F- transporters and urease regulatory proteins such as UreA, UreB, UreC, UreD, and UreG suggesting a role in defluoridation. Our findings provide new insights into the urease based MICP technology using a noble bacterium Proteus columbae MLN9 for fluoride removal

Arsenic burden from cooked rice in the populations of arsenic affected and nonaffected areas and Kolkata city in west-Bengal, India

Arsenic contamination of rice irrigated with contaminated groundwater contributes to the additional arsenic burden of the population where rice is the staple food. In an arsenic contaminated area, an experimental field-based study done on nine fields elucidated significant positive correlation between arsenic in irrigation water and soil, irrigation water and rice, and also soil and rice both for Boro (groundwater) and Aman (rainwater) rice. Speciation studies showed that for both Boro (cooked) and Aman (raw) rice from contaminated area, 90% of total recovered arsenic was inorganic. In arsenic contaminated, uncontaminated villages, and Kolkata city, daily quantities of arsenic ingested by adult population from cooked rice diet are equivalent to 6.5, 1.8, and 2.3 L, respectively, of drinking water containing WHO guideline value. In contaminated area, daily intake only from cooked Boro rice for 34.6% of the samples exceeded the WHO recommended MTDI value (2 mu g In-As day(-1) kg(-1) body wt), whereas daily intake from Aman rice was below MTDI value as was rice from uncontaminated areas and Kolkata city. Our study indicated that employing traditional rice cooking method as followed in Bengal delta and using water having arsenic <3 mu g L(-1) for cooking, actual exposure to arsenic from rice would be much less