Physics-Based Machine Learning Models Predict Carbon Dioxide Solubility in Chemically Reactive Deep Eutectic Solvents.

Carbon dioxide (CO2) is a detrimental greenhouse gas and is the main contributor to global warming. In addressing this environmental challenge, a promising approach emerges through the utilization of deep eutectic solvents (DESs) as an ecofriendly and sustainable medium for effective CO2 capture. Chemically reactive DESs, which form chemical bonds with the CO2, are superior to nonreactive, physically based DESs for CO2 absorption. However, there are no accurate computational models that provide accurate predictions of the CO2 solubility in chemically reactive DESs. Here, we develop machine learning (ML) models to predict the solubility of CO2 in chemically reactive DESs. As training data, we collected 214 data points for the CO2 solubility in 149 different chemically reactive DESs at different temperatures, pressures, and DES molar ratios from published work. The physics-driven input features for the ML models include σ-profile descriptors that quantify the relative probability of a molecular surface segment having a certain screening charge density and were calculated with the first-principle quantum chemical method COSMO-RS. We show here that, although COSMO-RS does not explicitly calculate chemical reaction profiles, the COSMO-RS-derived σ-profile features can be used to predict bond formation. Of the models trained, an artificial neural network (ANN) provides the most accurate CO2 solubility prediction with an average absolute relative deviation of 2.94% on the testing sets. Overall, this work provides ML models that can predict CO2 solubility precisely and thus accelerate the design and application of chemically reactive DESs.

Trimethylsilyldiazomethane Disassembly at a Three-Fold Symmetric Iron Site.

The reaction of equimolar trimethylsilyldiazomethyllithium (LiTMSD) with high spin (S = 2) PhB(AdIm)3FeCl (PhB(AdIm)3- = tris(3-adamantylimidazol-2-ylidene)phenylborate) affords the corresponding N-nitrilimido complex PhB(AdIm)3Fe-N═N═C(SiMe3). This complex can be converted to the thermodynamically more favorable C-isocyanoamido isomer PhB(AdIm)3Fe-C═N═N(SiMe3) by reaction with an additional equivalent of LiTMSD. While the iron(II) complexes are four-coordinate, the diazomethane is bound side-on in the iron(I) congener PhB(AdIm)3Fe(N,N'-κ2-N2C(H)Si(CH3)3). The latter complex adopts high spin (S = 3/2) ground state and features an unusually weak C-H bond. Photolysis of the iron(II) complexes induces N═N bond cleavage, with the iron(II) cyanide PhB(AdIm)3Fe-C≡N and iron(IV) nitride PhB(AdIm)3Fe≡N complexes being the major products of the reaction. The same products are obtained when the iron(I) complex is photolyzed or treated with a fluoride source. The trimethylsilyldiazomethane-derived ligand disassembly reactions are contrasted with those observed for related tris(carbene)amine complexes.

Association of Pharmacologic Treatment of Depression/Anxiety With Initial Patient-Reported Outcome Measures in Patients With Hip and Knee Osteoarthritis.

INTRODUCTION: Depression and anxiety are common comorbidities that may exacerbate osteoarthritis (OA)-related pain. We aim to evaluate the effect of pharmacologic treatment of depression/anxiety on hip and knee patient-reported outcome measures (PROMs). METHODS: A multi-institutional PROMs database was queried for patients with depression or anxiety and hip or knee OA who completed a PROMs questionnaire at an initial orthopaedic visit between January 2015 and March 2023. Data on demographics, comorbidities, and duration of pharmacologic treatment of depression/anxiety were obtained. Patients were stratified into three cohorts based on treatment duration. PROMs were compared across cohorts. RESULTS: Two thousand nine hundred sixty patients who completed PROMs at their initial orthopaedic visit had both OA and depression/anxiety. One hundred thirty-four (4.5%) received pharmacologic treatment of depression/anxiety for < 1 year, versus 196 (6.6%) for more than 1 year. In unadjusted analyses, patients with pharmacologic treatment had significantly lower Patient-Reported Outcomes Measurement Information System (PROMIS)-Physical (39.8 [IQR 34.9, 44.9] vs 42.3 [37.4, 47.7], P < 0.001) and PROMIS-Mental (43.5 [36.3, 50.8] vs 48.3 [41.1, 53.3], P < 0.001) scores than those without treatment. After adjusting for demographics and comorbidities, only differences in PROMIS-Mental scores remained statistically significant, with pharmacologic treatment associated with lower scores (ß = -2.26, 95% CI, [-3.29, -1.24], P < 0.001). On secondary analysis including duration of pharmacologic treatment, < 1 year of treatment was associated with significantly lower PROMIS-Mental scores than those not treated (ß = -4.20, 95% CI [-5.77, -2.62], P < 0.001) while scores of patients with more than 1 year of treatment did not differ significantly from those without treatment. CONCLUSION: :Our results indicate that pharmacologic treatment of depression/anxiety is associated with improved psychological health but not with improved physical symptoms related to OA. We observed a nonsignificant trend that patients with depression/anxiety who warrant pharmacologic treatment tend to have worse physical symptoms than those who do not; however, unadjusted analyses suggest this is a complex relationship beyond the isolated effect of pharmacologic treatment.

Differences in Baseline Physical Function and Mental Health PROM Scores in Patients With Foot and Ankle Conditions.

BACKGROUND: This study sought to establish normative values for baseline physical and mental health by foot and ankle diagnosis using validated PROMIS scores and to compare the correlation between these 2 outcomes across common diagnoses. Additionally, it investigated the effects associated with chronic vs acute conditions and specific diagnoses on mental health. METHODS: We reviewed baseline PROMIS Physical Function 10a (PF10a) and PROMIS Global-Mental (PGM) scores of 14,245 patients with one of the 10 most common foot and ankle diagnoses seen at our institution between 2016 and 2021. Pearson correlation coefficients were calculated to assess the relationship between PF10a and PGM by diagnosis. A multivariable regression model including age, sex, language, race, ethnicity, education level, income, and Charlson Comorbidity Index was used to determine the associated effect of diagnosis on PGM score. RESULTS: On unadjusted analysis, patients diagnosed with an ankle fracture had the lowest mean physical function, whereas patients with hallux valgus had the highest (PF10a = 33.9 vs 46.7, P < .001). Patients with foot/ankle osteoarthritis had the lowest mean self-reported mental health, whereas patients with hallux rigidus had the highest (PGM = 49.9 vs 53.4, P < .001). PF10a and PGM scores were significantly positively correlated for all diagnoses; the correlation was strongest in patients diagnosed with foot/ankle osteoarthritis or hammertoes (r = 0.511) and weakest in patients with ankle fractures (r = 0.232) or sprains (r = 0.280). Chronic conditions, including hammertoes (ß = -5.1, 95% CI [-5.8, -4.3], P < .001), foot/ankle osteoarthritis (ß = -5.0, 95% CI [-5.7, -4.3], P < .001), and hallux valgus (ß = -4.8, 95% CI [-5.5, -4.1], P < .001) were associated with the largest negative effects on patients' mental health. CONCLUSION: Self-reported physical function and mental health varied across common foot and ankle diagnoses and were more tightly correlated in chronic conditions. The associations between diagnosis and mental health scores appear larger for more chronic diagnoses, including those that are generally associated with relatively unimpaired physical function. LEVEL OF EVIDENCE: Level IV, retrospective, cross-sectional study.

Carbon Footprint of Minor Foot and Ankle Surgery: A Randomized Controlled Trial.

Background: Climate change poses a substantial threat to human health, and operating rooms (ORs) have an outsized environmental impact. The Program for Research in Sustainable Medicine (PRiSM) designed a protocol for minor foot and ankle surgery intended to reduce waste, streamline instrument trays, and minimize laundry. We conducted a randomized controlled trial to compare the carbon footprint of procedures performed using the PRiSM protocol vs a traditional protocol. Methods: Forty adult patients undergoing foreign body removal, hammertoe correction, toe amputation, hardware removal, mass excision, or gastrocnemius recession were randomized to the PRiSM or our "Traditional" protocol. The PRiSM protocol used a smaller instrument tray, fewer drapes and towels, and minimal positioning blankets. No changes were made to surgical site preparation or operative techniques. Environmental impact was estimated using the carbon footprint, measured in kilograms of carbon dioxide equivalents (CO2e). Emissions associated with OR waste, instrument processing, and laundry were calculated. Results: On average, PRiSM cases had a smaller carbon footprint than Traditional cases (17.3 kg CO2e [SD = 3.2] vs 20.6 kg CO2e [SD = 2.0], P < .001). Waste-associated emissions from PRiSM cases were reduced (16.0 kg CO2e [SD = 2.7] vs 18.4 kg CO2e [SD = 1.8], P = .002), as were modeled instrument processing-related emissions (0.34 vs 0.91 kg CO2e). One superficial surgical site infection occurred in each group. Conclusion: We found a small but statistically significant reduction in the environmental impact of minor foot and ankle surgery when using the PRiSM vs Traditional protocol. The environmental impact of these cases was dominated by plastic waste-related emissions. Orthopaedic surgeons should think critically about what components of their surgical setup are truly necessary for patient care, as minor changes in product utilization can have significant impacts on waste and greenhouse gas emissions. Level of Evidence: Level I, randomized controlled trial.

A Large Ankle Mass in a Figure Skater: A Case Report.

A 19-year-old male competitive figure skater presented to clinic with a 3-year history of right ankle swelling. Exam demonstrated a ~6cm diameter mass over the medial malleolus. MRI revealed a well-circumscribed fluid-filled mass. After failing conservative management, the patient underwent surgical excision. Anatomic pathology revealed a pseudocyst with pseudosynovial metaplasia, consistent with malleolar bursitis. Competitive figure skaters can develop significant medial malleolar bursitis due to excessive shear forces from ill-fitting skates. If non-operative management is ineffective, patients can be managed successfully with surgical excision. The patient made a full recovery and has returned to competitive skating without recurrence.

Primary Care Physician Preferences Regarding Communication from Orthopaedic Surgeons.

BACKGROUND: Musculoskeletal consultations constitute a growing portion of primary care physician (PCP) referrals. Optimizing communication between PCPs and orthopaedists can potentially reduce time spent in the electronic medical record (EMR) as well as physician burnout. Little is known about the preferences of PCPs regarding communication from orthopaedic surgeons. Hence, the present study investigated, across a large health network, the preferences of PCPs regarding communication from orthopaedists. METHODS: A total of 175 PCPs across 15 practices within our health network were surveyed. These providers universally utilized Epic as their EMR platform. Five-point, labeled Likert scales were utilized to assess the PCP-perceived importance of communication from orthopaedists in specific clinical scenarios. PCPs were further asked to report their preferred method of communication in each scenario and their overall interest in communication from orthopaedists. Logistic regression analyses were performed to determine whether any PCP characteristics were associated with the preferred method of communication and the overall PCP interest in communication from orthopaedists. RESULTS: A total of 107 PCPs (61.1%) responded to the survey. PCPs most commonly rated communication from orthopaedists as highly important in the scenario of an orthopaedist needing information from the PCP. In this scenario, PCPs preferred to receive an Epic Staff Message. Scenarios involving a recommendation for surgery, hospitalization, or a major clinical change were also rated as highly important. In these scenarios, an Epic CC'd Chart rather than a Staff Message was preferred. Increased after-hours EMR use was associated with diminished odds of having a high interest in communication from orthopaedists (odds ratio, 0.65; 95% confidence interval, 0.48 to 0.88; p = 0.005). Ninety-three PCPs (86.9%) reported spending 1 to 1.5 hours or more per day in Epic after normal clinical hours, and 27 (25.2%) spent >3 hours per day. Forty-six PCPs (43.0%) reported experiencing ≥1 symptom of burnout. CONCLUSIONS: There were distinct preferences among PCPs regarding clinical communication from orthopaedic surgeons. There was also evidence of substantial burnout and after-hours work effort by PCPs. These results may help to optimize communication between PCPs and orthopaedists while reducing the amount of time that PCPs spend in the EMR.

Accurate Machine Learning for Predicting the Viscosities of Deep Eutectic Solvents.

Deep eutectic solvents (DESs) are emerging as environmentally friendly designer solvents for mass transport and heat transfer processes in industrial applications; however, the lack of accurate tools to predict and thus control their viscosities under both a range of environmental factors and formulations hinders their general application. While DESs may serve as designer solvents, with nearly unlimited combinations, this unfortunately makes it experimentally infeasible to comprehensively measure the viscosities of all DESs of potential industrial interest. To assist in the design of DESs, we have developed several new machine learning (ML) models that accurately and rapidly predict the viscosities of a diverse group of DESs at different temperatures and molar ratios using, to date, one of the most comprehensive data sets containing the properties of over 670 DESs over a wide range of temperatures (278.15-385.25 K). Three ML models, including support vector regression (SVR), feed forward neural networks (FFNNs), and categorical boosting (CatBoost), were developed to predict DES viscosity as a function of temperature and molar ratio and contrasted with multilinear and two-factor polynomial regression baselines. Quantum chemistry-based, COSMO-RS-derived sigma profile (σ-profile) features were used as inputs for the ML models. The CatBoost model is excellent at externally predicting DES viscosity, as indicated by high R2 (0.99) and low root-mean-square-error (RMSE) and average absolute relative deviations (AARD) (5.22%) values for the testing data sets, and 98% of the data points lie within the 15% of AARD deviations. Furthermore, SHapley additive explanation (SHAP) analysis was employed to interpret the ML results and rationalize the viscosity predictions. The result is an ML approach that accurately predicts viscosity and will aid in accelerating the design of appropriate DESs for industrial applications.

Multi-Dimensional Wi-Fi Received Signal Strength Indicator Data Augmentation Based on Multi-Output Gaussian Process for Large-Scale Indoor Localization.

Location fingerprinting using Received Signal Strength Indicators (RSSIs) has become a popular technique for indoor localization due to its use of existing Wi-Fi infrastructure and Wi-Fi-enabled devices. Artificial intelligence/machine learning techniques such as Deep Neural Networks (DNNs) have been adopted to make location fingerprinting more accurate and reliable for large-scale indoor localization applications. However, the success of DNNs for indoor localization depends on the availability of a large amount of pre-processed and labeled data for training, the collection of which could be time-consuming in large-scale indoor environments and even challenging during a pandemic situation like COVID-19. To address these issues in data collection, we investigate multi-dimensional RSSI data augmentation based on the Multi-Output Gaussian Process (MOGP), which, unlike the Single-Output Gaussian Process (SOGP), can exploit the correlation among the RSSIs from multiple access points in a single floor, neighboring floors, or a single building by collectively processing them. The feasibility of MOGP-based multi-dimensional RSSI data augmentation is demonstrated through experiments using the hierarchical indoor localization model based on a Recurrent Neural Network (RNN)-i.e., one of the state-of-the-art multi-building and multi-floor localization models-and the publicly available UJIIndoorLoc multi-building and multi-floor indoor localization database. The RNN model trained with the UJIIndoorLoc database augmented with the augmentation mode of "by a single building", where an MOGP model is fitted based on the entire RSSI data of a building, outperforms the other two augmentation modes and results in the three-dimensional localization error of 8.42 m.

2023 Update in ambulatory general internal medicine.

The practice of outpatient medicine is demanding, encompasses a wide scope of practice, and leaves little time for internists to stay up to date with the current literature. This article reviews 5 studies published in 2022 and 2023 that have the potential to change the practice of outpatient medicine. Topics covered include chronic kidney disease, secondary cardiovascular disease, kidney stones, obesity, and lipid management.

Utilizing functional genomics in Saccharomyces cerevisiae to characterize food preservative compounds: A pilot study.

Chemical preservatives are ubiquitously used to suppress the growth of or kill microorganisms across numerous industries, including the food industry. Utilizing yeast functional genomic techniques, genes and their functions can be observed at a genomic scale to elucidate how environmental stressors (e.g., chemical preservatives) impact microbial survival. These types of chemical genomics approaches can reveal genetic mutations that result in preservative resistance or sensitivity, assist in identification of preservative mechanism of action, and can be used to compare different preservatives for rational design of preservative mixtures. In this proof-of-concept study, we performed deletion and high-copy genetic expression screens to identify mutants that confer drug resistance to sodium benzoate, potassium sorbate, rosemary extract, and Natamax. By observing overlapping mutant genes between genetic screens, we were able to identify functional overlap between chemical preservatives and begin to explain mechanisms of action for these compounds.

Drugging the entire human proteome: Are we there yet?

Each of the ∼20,000 proteins in the human proteome is a potential target for compounds that bind to it and modify its function. The 3D structures of most of these proteins are now available. Here, we discuss the prospects for using these structures to perform proteome-wide virtual HTS (VHTS). We compare physics-based (docking) and AI VHTS approaches, some of which are now being applied with large databases of compounds to thousands of targets. Although preliminary proteome-wide screens are now within our grasp, further methodological developments are expected to improve the accuracy of the results.

The Use of the Lateral Tibial Line to Assess Ankle Alignment: A Preliminary Investigation.

BACKGROUND: Although the medial clear space (MCS) is commonly used to assess talar alignment and ankle stability, its measurement is variable with multiple reported normal values. We have observed that the lateral tibial shaft is a reliable landmark to assess talar alignment. The objective of the current investigation was to determine the normal relationship of the lateral tibia to the superolateral talus using a tangent drawn inferiorly from the lateral tibial shaft, which we refer to as the "lateral tibial line" (LTL). METHODS: The relationship of the LTL to the superolateral talus was assessed by three reviewers on 99 standing ankle mortise radiographs in uninjured patients. This relationship was quantified by measuring the distance (in millimeters) between the LTL and the superolateral talus. In addition, the interobserver reliability of the LTL measurement was recorded and compared with that of the MCS. RESULTS: The median value for the distance between the superolateral talus and LTL was -0.50 mm with an interquartile range of -1.4 to 0.0 mm. The LTL was within 1 mm of the lateral talus in 176 of 297 reviewer measurements (59.3%). Moreover, it was either lateral to or at most 1 mm medial to the lateral talus in 90.9% of cases. The LTL measurement also demonstrated good interobserver reliability (0.764, 95% confidence interval, 0.670 to 0.834), similar to the measurement of MCS (0.742, 95% confidence interval, 0.539 to 0.846). CONCLUSIONS: The relationship between the LTL and superolateral talus is easily measured with good reliability for assessing the anatomic relationship of the tibia and talus. The LTL uncommonly fell more than 1 mm medial to the superolateral talus, as might be seen with displaced ankle fractures. These findings will hopefully serve as a basis for future studies evaluating its role in assessing lateral displacement and stability of isolated fibula fractures. LEVEL OF EVIDENCE: Level III, retrospective review.

Atomistic Simulations of Polydisperse Lignin Melts Using Simple Polydisperse Residue Input Generator.

Understanding the physics of lignin will help rationalize its function in plant cell walls as well as aiding practical applications such as deriving biofuels and bioproducts. Here, we present SPRIG (Simple Polydisperse Residue Input Generator), a program for generating atomic-detail models of random polydisperse lignin copolymer melts i.e., the state most commonly found in nature. Using these models, we use all-atom molecular dynamics (MD) simulations to investigate the conformational and dynamic properties of polydisperse melts representative of switchgrass (Panicum virgatum L.) lignin. Polydispersity, branching and monolignol sequence are found to not affect the calculated glass transition temperature, Tg. The Flory-Huggins scaling parameter for the segmental radius of gyration is 0.42 ± 0.02, indicating that the chains exhibit statistics that lie between a globular chain and an ideal Gaussian chain. Below Tg the atomic mean squared displacements are independent of molecular weight. In contrast, above Tg, they decrease with increasing molecular weight. Therefore, a monodisperse lignin melt is a good approximation to this polydisperse lignin when only static properties are probed, whereas the molecular weight distribution needs to be considered while analyzing lignin dynamics.

Intraarticular Injections in the Foot and Ankle: Medication Selection Patterns and Perceived Risk Of Chondrotoxicity.

Background: Intraarticular corticosteroid injections (ICIs) are widely used to treat foot and ankle conditions. Although laboratory studies indicate certain corticosteroids and local anesthetics used in ICIs are associated with chondrotoxic effects, and selected agents such as ropivacaine and triamcinolone may have less of these features, clinical evidence is lacking. We aimed to identify the patterns of drug selection, perceptions of injectate chondrotoxicity, and rationale for medication choice among surgeons in the American Orthopaedic Foot & Ankle Society (AOFAS). Methods: An e-survey including demographics, practice patterns, and rationale was disseminated to 2011 AOFAS members. Frequencies and percentages were calculated for demographic data, anesthetic and steroid choice, rationale for injectate choice, and perception of chondrotoxicity. Bivariate analysis was used to identify practice patterns significantly associated with perceptions of injectate risk and rationale. Results: In total, 387 surveys were completed. Lidocaine and triamcinolone were the most common anesthetic and corticosteroid used (51.2% and 39.3%, respectively). Less than half of respondents felt corticosteroids or local anesthetics bear risk of chondrotoxicity. Respondents agreeing that corticosteroids are chondrotoxic were more likely to use triamcinolone (P = .037). Respondents agreeing local anesthetics risk chondrotoxicity were less likely to use lidocaine (P = .023). Respondents choosing a local anesthetic based on literature were more likely to use ropivacaine (P < .001). Conclusion: Corticosteroid and local anesthetic use in ICIs varied greatly. Rationale for ICI formulation was also variable, as the clinical implications are largely unknown. Those who recognized potential chondrotoxicity and who chose based on literature were more likely to choose ropivacaine and triamcinolone, as reflected in the basic science literature. Further clinical studies are needed to establish guidelines that shape foot and ankle ICI practices based on scientific evidence and reduce the variation identified by this study. Level of Evidence: Level IV, cross-sectional survey study.

Efficiency and perceived safety of foot and ankle procedures performed on the preoperative stretcher versus operating room table.

BACKGROUND: Foot and ankle surgeons often perform minor surgeries on the preoperative stretcher instead of the operating room table. We examined whether stretcher-based and operating room table-based procedures differed with respect to operating room efficiency and staff perceptions. METHODS: We retrospectively reviewed medical records of patients undergoing minor foot and ankle surgery at an ambulatory surgery centre. We collected 'time to start', the duration between patient arrival in the operating room and incision time, and 'time to exit', the duration between procedure end time and patient exit from the operating room. Staff were surveyed regarding their perceptions of stretcher-based and operating room table-based procedures. RESULTS: 'Time to start' was significantly shorter for stretcher-based procedures, but 'time to exit' was not. Seventeen (81%) staff members thought stretcher-based procedures increased operating room efficiency. Thirteen (62%) thought stretcher-based procedures bettered staff safety. Nineteen (91%) thought stretcher-based procedures were equivalent to or better than operating room table-based procedures for patient safety. Most (67%) would recommend stretcher-based procedures. CONCLUSION: We found small but significant time savings associated with stretcher-based procedures. Without adapting surgical scheduling practices, the impact of stretcher-based procedures on overall operating room efficiency is questionable. Nevertheless, the majority of OR staff think stretcher-based procedures increase OR efficiency and are safer for staff. LEVEL OF EVIDENCE: Level IV, Retrospective case series.

Targeted inhibition of MASTL kinase activity induces apoptosis in breast cancer.

Microtubule-associated serine/threonine kinase-like (MASTL) (or Greatwall kinase (GWL)) is an important cell cycle regulating kinase that regulates the G2-M transition. Uncontrolled MASTL activity is implicated in breast cancer progression. To date, very few inhibitors have been reported against this protein. Here, structure-based computational modeling indicates that the natural product flavopiridol (FLV) binds strongly to MASTL and these results are validated using molecular dynamics simulation studies. An in vitro kinase assay reveals an EC50 (effective concentration) value of FLV to be 82.1 nM and a better IC50 compared to the positive reference compound, staurosporine. FLV is found to inhibit MASTL kinase activity, arresting the cell growth in the G1 phase and inducing apoptosis in breast cancer cells. Consistent with these results differential gene expression obtained using RNA sequencing studies, and validated by RT PCR and immunoblot analysis, indicate that MASTL inhibition induces cell cycle arrest and apoptotic-related genes. Furthermore, metastasis- and inflammation-related genes are downregulated. Thus, the deregulation of MASTL signaling pathways on targeted inhibition of its kinase activity is revealed. This study lays a strong foundation for investigating FLV as a lead compound in breast cancer therapeutics.

Comparative Assessment of Pose Prediction Accuracy in RNA-Ligand Docking.

Structure-based virtual high-throughput screening is used in early-stage drug discovery. Over the years, docking protocols and scoring functions for protein-ligand complexes have evolved to improve the accuracy in the computation of binding strengths and poses. In the past decade, RNA has also emerged as a target class for new small-molecule drugs. However, most ligand docking programs have been validated and tested for proteins and not RNA. Here, we test the docking power (pose prediction accuracy) of three state-of-the-art docking protocols on 173 RNA-small molecule crystal structures. The programs are AutoDock4 (AD4) and AutoDock Vina (Vina), which were designed for protein targets, and rDock, which was designed for both protein and nucleic acid targets. AD4 performed relatively poorly. For RNA targets for which a crystal structure of a bound ligand used to limit the docking search space is available and for which the goal is to identify new molecules for the same pocket, rDock performs slightly better than Vina, with success rates of 48% and 63%, respectively. However, in the more common type of early-stage drug discovery setting, in which no structure of a ligand-target complex is known and for which a larger search space is defined, rDock performed similarly to Vina, with a low success rate of ∼27%. Vina was found to have bias for ligands with certain physicochemical properties, whereas rDock performs similarly for all ligand properties. Thus, for projects where no ligand-protein structure already exists, Vina and rDock are both applicable. However, the relatively poor performance of all methods relative to protein-target docking illustrates a need for further methods refinement.