MTD-Diorama: Moving Target Defense Visualization Engine for Systematic Cybersecurity Strategy Orchestration.

With the advancement in information and communication technology, modern society has relied on various computing systems in areas closely related to human life. However, cyberattacks are also becoming more diverse and intelligent, with personal information and human lives being threatened. The moving target defense (MTD) strategy was designed to protect mission-critical systems from cyberattacks. The MTD strategy shifted the paradigm from passive to active system defense. However, there is a lack of indicators that can be used as a reference when deriving general system components, making it difficult to configure a systematic MTD strategy. Additionally, even when selecting system components, a method to confirm whether the systematic components are selected to respond to actual cyberattacks is needed. Therefore, in this study, we surveyed and analyzed existing cyberattack information and MTD strategy research results to configure a component dataset. Next, we found the correlation between the cyberattack information and MTD strategy component datasets and used this to design and implement the MTD-Diorama data visualization engine to configure a systematic MTD strategy. Through this, researchers can conveniently identify the attack surface contained in cyberattack information and the MTD strategies that can respond to each attack surface. Furthermore, it will allow researchers to configure more systematic MTD strategies that can be used universally without being limited to specific computing systems.

Identification of inhibitor binding hotspots in Acinetobacter baumannii ß-ketoacyl acyl carrier protein synthase III using molecular dynamics simulation.

Acinetobacter baumannii is a gram-negative bacterium that is rapidly developing drug resistance due to the abuse of antibiotics. The emergence of multidrug-resistant A. baumannii has greatly contributed to the urgency of developing new antibiotics. Previously, we had discovered two potent inhibitors of A. baumannii ß-ketoacyl acyl carrier protein synthase III (abKAS III), YKab-4 and YKab-6, which showed potent activity against A. baumannii. In addition, we have reported the crystal structure of abKAS III. In the present study, we investigated the binding between abKAS III and its inhibitors by docking simulation. Molecular dynamics (MD) simulations were performed using docked inhibitor models to identify the hotspot residues related to inhibitor binding. The binding free energies estimated using the MD simulations suggest that residues I198 and F260 of abKAS III serve as the inhibitor binding hotspots. I198, found to be responsible for mediating hydrophobic interactions with inhibitors, had the strongest residual binding energy among all abKAS III residues. We modeled glutamine substitutions of residues I198 and F260 and estimated the relative binding energies of the I198Q and F260Q variants. The results confirmed that I198 and F260 are the key inhibitor binding residues. The roles of the key residues in inhibitor binding, i.e. F260 in the α9 helix and the I198 in the ß6ß7 loop region, were investigated using principal component analysis (PCA). PCA revealed the structural changes resulting from the abKAS III I198Q and F260Q mutations and described the essential dynamics of the α9 helix. In addition, the results suggest that the ß6ß7 loop region may act as a gate keeper for ligand binding. Hydrophobic interactions involving I198 and F260 in abKAS III appear to be essential for the binding of the inhibitors YKab-4 and YKab-6. In conclusion, this study provides valuable information for the rational design of antibiotics via the inhibition of abKAS III.

PMFF: Development of a Physics-Based Molecular Force Field for Protein Simulation and Ligand Docking.

The physics-based molecular force field (PMFF) was developed by integrating a set of potential energy functions in which each term in an intermolecular potential energy function is derived based on experimental values, such as the dipole moments, lattice energy, proton transfer energy, and X-ray crystal structures. The term "physics-based" is used to emphasize the idea that the experimental observables that are considered to be the most relevant to each term are used for the parameterization rather than parameterizing all observables together against the target value. PMFF uses MM3 intramolecular potential energy terms to describe intramolecular interactions and includes an implicit solvation model specifically developed for the PMFF. We evaluated the PMFF in three ways. We concluded that the PMFF provides reliable information based on the structure in a biological system and interprets the biological phenomena accurately by providing more accurate evidence of the biological phenomena.

Development of a wheeled walker braking device using the four-bar mechanism.

The elderly population in many countries has been rising rapidly, and falls are a serious event many elderly people experience. Assistive equipment is actively used to reduce falls among elderly people. Popular types of assistive equipment include canes, electric wheelchairs, and wheeled walkers. Wheeled walkers support the body of elderly people, making their gait comfortable as they age or recover from injuries. Wheeled walkers may be equipped with hand brakes; however, frail older people may experience difficulty using such hand brakes, as they require force to operate. Thus, in the present study, a braking method using a wire connected to a user's belt or clothes was designed and implemented; if the tension of the wire connecting the safety device and the user exceeds a critical value, the wheeled walker brakes, which can prevent the rapid motion of walkers. Two feasibility tests of the wheeled walker with the braking device were conducted: one with 10 healthy adults in their 20s and the other with 10 elderly people over 65 years of age; the tests measured the braking time and speed control using a speed measuring device. The results of the first and second feasibility tests demonstrated that the average braking time of participants was 50.3 ms and 50.7 ms, respectively. All participants in the feasibility tests succeeded in the speed control test. Thus, based on the results, the braking device on the wheeled walker worked properly.

In Silico Site-Directed Mutagenesis Informs Species-Specific Predictions of Chemical Susceptibility Derived From the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) Tool.

Chemical hazard assessment requires extrapolation of information from model organisms to all species of concern. The Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool was developed as a rapid, cost-effective method to aid cross-species extrapolation of susceptibility to chemicals acting on specific protein targets through evaluation of protein structural similarities and differences. The greatest resolution for extrapolation of chemical susceptibility across species involves comparisons of individual amino acid residues at key positions involved in protein-chemical interactions. However, a lack of understanding of whether specific amino acid substitutions among species at key positions in proteins affect interaction with chemicals made manual interpretation of alignments time consuming and potentially inconsistent. Therefore, this study used in silico site-directed mutagenesis coupled with docking simulations of computational models for acetylcholinesterase (AChE) and ecdysone receptor (EcR) to investigate how specific amino acid substitutions impact protein-chemical interaction. This study found that computationally derived substitutions in identities of key amino acids caused no change in protein-chemical interaction if residues share the same side chain functional properties and have comparable molecular dimensions, while differences in these characteristics can change protein-chemical interaction. These findings were considered in the development of capabilities for automatically generated species-specific predictions of chemical susceptibility in SeqAPASS. These predictions for AChE and EcR were shown to agree with SeqAPASS predictions comparing the primary sequence and functional domain sequence of proteins for more than 90% of the investigated species, but also identified dramatic species-specific differences in chemical susceptibility that align with results from standard toxicity tests. These results provide a compelling line of evidence for use of SeqAPASS in deriving screening level, species-specific, susceptibility predictions across broad taxonomic groups for application to human and ecological hazard assessment.

Incorporation of Hydrogen Bond Angle Dependency into the Generalized Solvation Free Energy Density Model.

To describe the physically realistic solvation free energy surface of a molecule in a solvent, a generalized version of the solvation free energy density (G-SFED) calculation method has been developed. In the G-SFED model, the contribution from the hydrogen bond (HB) between a solute and a solvent to the solvation free energy was calculated as the product of the acidity of the donor and the basicity of the acceptor of an HB pair. The acidity and basicity parameters of a solute were derived using the summation of acidities and basicities of the respective acidic and basic functional groups of the solute, and that of the solvent was experimentally determined. Although the contribution of HBs to the solvation free energy could be evenly distributed to grid points on the surface of a molecule, the G-SFED model was still inadequate to describe the angle dependency of the HB of a solute with a polarizable continuum solvent. To overcome this shortcoming of the G-SFED model, the contribution of HBs was formulated using the geometric parameters of the grid points described in the HB coordinate system of the solute. We propose an HB angle dependency incorporated into the G-SFED model, i.e., the G-SFED-HB model, where the angular-dependent acidity and basicity densities are defined and parametrized with experimental data. The G-SFED-HB model was then applied to calculate the solvation free energies of organic molecules in water, various alcohols and ethers, and the log P values of diverse organic molecules, including peptides and a protein. Both the G-SFED model and the G-SFED-HB model reproduced the experimental solvation free energies with similar accuracy, whereas the distributions of the SFED on the molecular surface calculated by the G-SFED and G-SFED-HB models were quite different, especially for molecules having HB donors or acceptors. Since the angle dependency of HBs was included in the G-SFED-HB model, the SFED distribution of the G-SFED-HB model is well described as compared to that of the G-SFED model.

A Self-Powered Sensor Mimicking Slow- and Fast-Adapting Cutaneous Mechanoreceptors.

Highly efficient human skin systems transmit fast adaptive (FA) and slow adaptive (SA) pulses selectively or consolidatively to the brain for a variety of external stimuli. The integrated analysis of these signals determines how humans perceive external physical stimuli. Here, a self-powered mechanoreceptor sensor based on an artificial ion-channel system combined with a piezoelectric film is presented, which can simultaneously implement FA and SA pulses like human skin. This device detects stimuli with high sensitivity and broad frequency band without external power. For the feasibility study, various stimuli are measured or detected. Vital signs such as the heart rate and ballistocardiogram can be measured simultaneously in real time. Also, a variety of stimuli such as the mechanical stress, surface roughness, and contact by a moving object can be distinguished and detected. This opens new scientific fields to realize the somatic cutaneous sensor of the real skin. Moreover, this new sensing scheme inspired by natural sensing structures is able to mimic the five senses of living creatures.

A novel one arm motorized walker for hemiplegic stroke survivors: a feasibility study.

BACKGROUND: A hemiplegic stroke survivor with a moderate to severe gait disturbance may have difficulty walking using a one-arm walker. This study aimed to test the safety and feasibility of a prototype one-arm motorized walker that uses a power-driven device to provide gait assistance to hemiplegic stroke survivors with moderate to severe gait disturbances. METHODS: A one-arm motorized walker with a power-driven device was developed and tested with respect to 10 distinct variables, including weight, degrees of freedom, handle, handle substitution function, two-sided use function, variable handle height, redirecting function, electric moving parts through the handle control, brake function using the handle control, folding chairs, and design stability. Its safety and feasibility were tested in 19 hemiplegic stroke individuals using the Likert scale and a simple interview. RESULTS: The walker consists of a frame platform including a handle, electric motor for driving, one wheel for driving, two wheels for turning, unlocking sensor, driving button, and turning buttons. The walker is programmed so that a touch sensor in the handle can unlock the locking system. Furthermore, it is programmed so that a user can propel it by pushing the handle downward or pressing a button and can control directions for turning right or left by pressing buttons. Safety and performance testing was achieved for 10 separate variables, and a Likert scale score of 3.5 of 5 was recorded. CONCLUSION: This walker's novel design was developed for hemiplegic stroke survivors with moderate to severe gait disturbances. Our findings indicate that the walker is both safe and feasible for providing walking assistance to hemiplegic stroke survivors and establish the potential advantages of the one-arm motorized walker.

3D-QSAR study of steroidal and azaheterocyclic human aromatase inhibitors using quantitative profile of protein-ligand interactions.

Aromatase is a member of the cytochrome P450 superfamily responsible for a key step in the biosynthesis of estrogens. As estrogens are involved in the control of important reproduction-related processes, including sexual differentiation and maturation, aromatase is a potential target for endocrine disrupting chemicals as well as breast cancer therapy. In this work, 3D-QSAR combined with quantitative profile of protein-ligand interactions was employed in the identification and characterization of critical steric and electronic features of aromatase-inhibitor complexes and the estimation of their quantitative contribution to inhibition potency. Bioactivity data on pIC50 values of 175 steroidal and 124 azaheterocyclic human aromatase inhibitors (AIs) were used for the 3D-QSAR analysis. For the quantitative description of the effects of the hydrophobic contact and nitrogen-heme-iron coordination on aromatase inhibition, the hydrophobicity density field model and the smallest dual descriptor Δf(r) S were introduced, respectively. The model revealed that hydrophobic contact and nitrogen-heme-iron coordination primarily determines inhibition potency of steroidal and azaheterocyclic AIs, respectively. Moreover, hydrogen bonds with key amino acid residues, in particular Asp309 and Met375, and interaction with the heme-iron are required for potent inhibition. Phe221 and Thr310 appear to be quite flexible and adopt different conformations according to a substituent at 4- or 6-position of steroids. Flexible docking results indicate that proper representation of the residues' flexibility is critical for reasonable description of binding of the structurally diverse inhibitors. Our results provide a quantitative and mechanistic understanding of inhibitory activity of steroidal and azaheterocyclic AIs of relevance to adverse outcome pathway development and rational drug design.

A novel hinged ankle foot orthosis for gait performance in chronic hemiplegic stroke survivors: a feasibility study.

Stroke survivors with gait disturbances may use ankle foot orthoses (AFOs). However, most AFOs come in one-piece styles, which make it difficult for spasticity-affected stroke survivors to don. AFOs are also limited since they do not properly prevent ankle joint for foot drop by itself. Therefore, the present study developed a novel hinged AFO by adding a locking device to a hinged joint. We then tested its feasibility in 9 hemiplegic stroke survivors by investigating temporal-spatial gait parameters using the GAITRite in the following 3 conditions: no AFO, traditional AFO, and novel hinged AFO. There was no significant difference in spatiotemporal gait parameters among the different conditions. There were greater decreases in gait velocity, cadence, step length, and stride length in the novel hinged AFO group than in the no AFO and traditional AFO groups. This novel hinged AFO was developed to prevent foot drop. However, the AFO did not show significant differences in gait parameters because it consists of metal with extra weight and volume. Functionally, it prevented foot drop. It also improved convenience by its releasable design. Thus, further studies are needed to develop an AFO that improves gait and is convenient to use for hemiplegic stroke survivors.

Comparison of trunk electromyographic muscle activity depends on sitting postures.

BACKGROUND: Different postural positions can be characterized by the activation and relative contributions of different postural muscles, and may variously contribute to the recovery from or worsening of chronic lower back pain. OBJECTIVE: The present study aimed to investigates trunk muscle activities in four types of seated postures: cross-legged, long, side, and W-shaped. METHODS: Eight healthy adults participated in the study. Trunk muscle activities of the external oblique (EO), rectus abdominis (RA), latissimus dorsi (LD), and erector spinae (ES) muscles in each of the sitting postures including cross-legged, long, side, and W-shaped were collected utilizing surface electromyography (sEMG). The mean sEMG signals in each of the sitting postures were used for statistical comparisons. RESULTS: There were no significant differences in electromyographic muscle activity of EO, RA, LD, and ES in the four postures (p > 0.05). However, in the W-shape sitting posture, the left LD showed the greatest electromyographic muscle activity, followed by the right LD and left EO, respectively. The right and left LD in the long sitting posture and left ES in the side sitting posture showed greater electromyographic muscle activity than that of other muscles. CONCLUSION: Based on the results, trunk muscle activity did not significantly differ between the four types of sitting postures. However, our study is limited by its experimental method and sample size. Thus, in the Future, further study will be needed.

Structure-Based Understanding of Binding Affinity and Mode of Estrogen Receptor α Agonists and Antagonists.

The flexible hydrophobic ligand binding pocket (LBP) of estrogen receptor α (ERα) allows the binding of a wide variety of endocrine disruptors. Upon ligand binding, the LBP reshapes around the contours of the ligand and stabilizes the complex by complementary hydrophobic interactions and specific hydrogen bonds with the ligand. Here we present a framework for quantitative analysis of the steric and electronic features of the human ERα-ligand complex using three dimensional (3D) protein-ligand interaction description combined with 3D-QSAR approach. An empirical hydrophobicity density field is applied to account for hydrophobic contacts of ligand within the LBP. The obtained 3D-QSAR model revealed that hydrophobic contacts primarily determine binding affinity and govern binding mode with hydrogen bonds. Several residues of the LBP appear to be quite flexible and adopt a spectrum of conformations in various ERα-ligand complexes, in particular His524. The 3D-QSAR was combined with molecular docking based on three receptor conformations to accommodate receptor flexibility. The model indicates that the dynamic character of the LBP allows accommodation and stable binding of structurally diverse ligands, and proper representation of the protein flexibility is critical for reasonable description of binding of the ligands. Our results provide a quantitative and mechanistic understanding of binding affinity and mode of ERα agonists and antagonists that may be applicable to other nuclear receptors.

Fatigue of human dentin by cyclic loading and during oral biofilm challenge.

Fatigue caused by the cyclic loads of mastication and acid attack caused by the excretion of oral biofilms are two of the most critical challenges to the success of dental restorations and their clinical service life. The objective of this investigation was to evaluate the fatigue strength of human dentin when exposed to a simultaneous challenge of cyclic loading and acidic attack from oral bacteria. Rectangular beams of coronal dentin were obtained from third molars and subjected to cyclic flexural loading while exposed to an in-vitro microcosm biofilm model. Two different cariogenic protocols were considered and results were compared with those for control samples evaluated at neutral pH. According to the fatigue life distributions, dentin exposed to the biofilm model with 2.0% sucrose supplements pulsed twice per day caused a significant reduction in the fatigue strength (p < 0.001) with respect to 0.2% sucrose supplements pulsed once a day, and the control environment (without biofilm). The endurance limit after biofilm exposure was 20 MPa, which is 60% lower than that of the control environment without biofilm (50 MPa). Biofilm attack of dentin increases the likelihood of restored tooth failures by fatigue and after only modest periods of exposure. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1978-1985, 2017.

A mechanism-based 3D-QSAR approach for classification and prediction of acetylcholinesterase inhibitory potency of organophosphate and carbamate analogs.

Organophosphate (OP) and carbamate esters can inhibit acetylcholinesterase (AChE) by binding covalently to a serine residue in the enzyme active site, and their inhibitory potency depends largely on affinity for the enzyme and the reactivity of the ester. Despite this understanding, there has been no mechanism-based in silico approach for classification and prediction of the inhibitory potency of ether OPs or carbamates. This prompted us to develop a three dimensional prediction framework for OPs, carbamates, and their analogs. Inhibitory structures of a compound that can form the covalent bond were identified through analysis of docked conformations of the compound and its metabolites. Inhibitory potencies of the selected structures were then predicted using a previously developed three dimensional quantitative structure-active relationship. This approach was validated with a large number of structurally diverse OP and carbamate compounds encompassing widely used insecticides and structural analogs including OP flame retardants and thio- and dithiocarbamate pesticides. The modeling revealed that: (1) in addition to classical OP metabolic activation, the toxicity of carbamate compounds can be dependent on biotransformation, (2) OP and carbamate analogs such as OP flame retardants and thiocarbamate herbicides can act as AChEI, (3) hydrogen bonds at the oxyanion hole is critical for AChE inhibition through the covalent bond, and (4) π-π interaction with Trp86 is necessary for strong inhibition of AChE. Our combined computation approach provided detailed understanding of the mechanism of action of OP and carbamate compounds and may be useful for screening a diversity of chemical structures for AChE inhibitory potency.

Controlled MoS2 layer etching using CF4 plasma.

A few-layered molybdenum disulfide (MoS2) thin film grown by plasma enhanced chemical vapor deposition was etched using a CF4 inductively coupled plasma, and the possibility of controlling the MoS2 layer thickness to a monolayer of MoS2 over a large area substrate was investigated. In addition, damage and contamination of the remaining MoS2 layer surface after etching and a possible method for film recovery was also investigated. The results from Raman spectroscopy and atomic force microscopy showed that one monolayer of MoS2 was etched by exposure to a CF4 plasma for 20 s after an initial incubation time of 20 s, i.e., the number of MoS2 layers could be controlled by exposure to the CF4 plasma for a certain processing time. However, XPS data showed that exposure to CF4 plasma induced a certain amount of damage and contamination by fluorine of the remaining MoS2 surface. After exposure to a H2S plasma for more than 10 min, the damage and fluorine contamination of the etched MoS2 surface could be effectively removed.

Development of 3D-QSAR Model for Acetylcholinesterase Inhibitors Using a Combination of Fingerprint, Molecular Docking, and Structure-Based Pharmacophore Approaches.

Acetylcholinesterase (AChE), a serine hydrolase vital for regulating the neurotransmitter acetylcholine in animals, has been used as a target for drugs and pesticides. With the increasing availability of AChE crystal structures, with or without ligands bound, structure-based approaches have been successfully applied to AChE inhibitors (AChEIs). The major limitation of these approaches has been the small applicability domain due to the lack of structural diversity in the training set. In this study, we developed a 3 dimensional quantitative structure-activity relationship (3D-QSAR) for inhibitory activity of 89 reversible and irreversible AChEIs including drugs and insecticides. A 3D-fingerprint descriptor encoding protein-ligand interactions was developed using molecular docking and structure-based pharmacophore to rationalize the structural requirements responsible for the activity of these compounds. The obtained 3D-QSAR model exhibited high correlation value (R(2) = 0.93) and low mean absolute error (MAE = 0.32 log units) for the training set (n = 63). The model was predictive across a range of structures as shown by the leave-one-out cross-validated correlation coefficient (Q(2) = 0.89) and external validation results (n = 26, R(2) = 0.89, and MAE = 0.38 log units). The model revealed that the compounds with high inhibition potency had proper conformation in the active site gorge and interacted with key amino acid residues, in particular Trp84 and Phe330 at the catalytic anionic site, Trp279 at the peripheral anionic site, and Gly118, Gly119, and Ala201 at the oxyanion hole. The resulting universal 3D-QSAR model provides insight into the multiple molecular interactions determining AChEI potency that may guide future chemical design and regulation of toxic AChEIs.

Controlled Layer-by-Layer Etching of MoS2.

Two-dimensional (2D) metal dichalcogenides like molybdenum disulfide (MoS2) may provide a pathway to high-mobility channel materials that are needed for beyond-complementary metal-oxide-semiconductor (CMOS) devices. Controlling the thickness of these materials at the atomic level will be a key factor in the future development of MoS2 devices. In this study, we propose a layer-by-layer removal of MoS2 using the atomic layer etching (ALET) that is composed of the cyclic processing of chlorine (Cl)-radical adsorption and argon (Ar)(+) ion-beam desorption. MoS2 etching was not observed with only the Cl-radical adsorption or low-energy (<20 eV) Ar(+) ion-beam desorption steps; however, the use of sequential etching that is composed of the Cl-radical adsorption step and a subsequent Ar(+) ion-beam desorption step resulted in the complete etching of one monolayer of MoS2. Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM) indicated the removal of one monolayer of MoS2 with each ALET cycle; therefore, the number of MoS2 layers could be precisely controlled by using this cyclical etch method. In addition, no noticeable damage or etch residue was observed on the exposed MoS2.

Influence of light touch using the fingertips on postural stability of poststroke patients.

[Purpose] The purpose of this study was to investigate the influence of fingertip light touch on the postural control in poststroke patients. [Subjects] In the study, the subjects were recruited through a rehabilitation hospital, and 21 patients were screened from among 30 volunteers. [Methods] The subjects participated in an experiment that measured postural sway during the static standing posture without light touch and postural sway during the static standing posture with light touch as follows: visual information not blocked without light touch, visual information blocked without light touch, visual information blocked with light touch using fingertips, and visual information not blocked with light touch using fingertips. The measurements were performed using a force platform. The variables measured by the force platform included sway velocities of the COP in the anterior and posterior directions and, medial and lateral directions and sway velocity moments. [Results] In the results of the study, there were significant differences between the state without light touch and state with light touch in terms of the postural sway velocity and velocity moment under all conditions. The rate of decease of the sway velocity and moment velocity under the eyes closed condition were higher compared with those under the eyes open condition. [Conclusion] Through this study, we confirmed the influence of fingertip light touch on the decrease in postural sway. The results show that active light touch may be supplemental means of improving postural sway in stroke patients.

Human nephrotoxicity prediction models for three types of kidney injury based on data sets of pharmacological compounds and their metabolites.

The kidney is the most important organ for the excretion of pharmaceuticals and their metabolites. Among the complex structures of the kidney, the proximal tubule and renal interstitium are major targets of nephrotoxins. Despite its importance, there are only a few in silico models for predicting human nephrotoxicity for drug candidates. Here, we present quantitative structure-activity relationship (QSAR) models for three common patterns of drug-induced kidney injury, i.e., tubular necrosis, interstitial nephritis, and tubulo-interstitial nephritis. A support vector machine (SVM) was used to build the binary classification models of nephrotoxin versus non-nephrotoxin with eight fingerprint descriptors. To build the models, we constructed two types of data sets, i.e., parent compounds of pharmaceuticals (251 nephrotoxins and 387 non-nephrotoxins) and their major urinary metabolites (307 nephrotoxins and 233 non-nephrotoxins). Information on the nephrotoxicity of the pharmaceuticals was taken from clinical trial and postmarketing safety data. Though the mechanisms of nephrotoxicity are very complex, by using the metabolite information, the predictive accuracies of the best models for each type of kidney injury were better than 83% for external validation sets. Software to predict nephrotoxicity is freely available from our Web site at http://bmdrc.org/DemoDownload .

A generalized G-SFED continuum solvation free energy calculation model.

An empirical continuum solvation model, solvation free energy density (SFED), has been developed to calculate solvation free energies of a molecule in the most frequently used solvents. A generalized version of the SFED model, generalized-SFED (G-SFED), is proposed here to calculate molecular solvation free energies in virtually any solvent. G-SFED provides an accurate and fast generalized framework without a complicated description of a solution. In the model, the solvation free energy of a solute is represented as a linear combination of empirical functions of the solute properties representing the effects of solute on various solute-solvent interactions, and the complementary solvent effects on these interactions were reflected in the linear expansion coefficients with a few solvent properties. G-SFED works well for a wide range of sizes and polarities of solute molecules in various solvents as shown by a set of 5,753 solvation free energies of diverse combinations of 103 solvents and 890 solutes. Octanol-water partition coefficients of small organic compounds and peptides were calculated with G-SFED with accuracy within 0.4 log unit for each group. The G-SFED computation time depends linearly on the number of nonhydrogen atoms (n) in a molecule, O(n).