Photo-actuators via epitaxial growth of microcrystal arrays in polymer membranes.

Photomechanical crystals composed of three-dimensionally ordered and densely packed photochromes hold promise for high-performance photochemical actuators. However, bulk crystals with high structural ordering are severely limited in their flexibility, resulting in poor processibility and a tendency to fragment upon light exposure, while previous nano- or microcrystalline composites have lacked global alignment. Here we demonstrate a photon-fuelled macroscopic actuator consisting of diarylethene microcrystals in a polyethylene terephthalate host matrix. These microcrystals survive large deformations and show a high degree of three-dimensional ordering dictated by the anisotropic polyethylene terephthalate, which critically also has a similar stiffness. Overall, these ordered and compliant composites exhibit rapid response times, sustain a performance of over at least hundreds of cycles and generate work densities exceeding those of single crystals. Our composites represent the state-of-the-art for photochemical actuators and enable properties unattainable by single crystals, such as controllable, reversible and abrupt jumping (photosalient behaviour).

Interactive Quantum Chemistry Enabled by Machine Learning, Graphical Processing Units, and Cloud Computing.

Modern quantum chemistry algorithms are increasingly able to accurately predict molecular properties that are useful for chemists in research and education. Despite this progress, performing such calculations is currently unattainable to the wider chemistry community, as they often require domain expertise, computer programming skills, and powerful computer hardware. In this review, we outline methods to eliminate these barriers using cutting-edge technologies. We discuss the ingredients needed to create accessible platforms that can compute quantum chemistry properties in real time, including graphical processing units-accelerated quantum chemistry in the cloud, artificial intelligence-driven natural molecule input methods, and extended reality visualization. We end by highlighting a series of exciting applications that assemble these components to create uniquely interactive platforms for computing and visualizing spectra, 3D structures, molecular orbitals, and many other chemical properties.

Kinetic View of Enzyme Catalysis from Enhanced Sampling QM/MM Simulations.

The rate constants of enzyme-catalyzed reactions (kcat) are often approximated from the barrier height of the reactive step. We introduce an enhanced sampling QM/MM approach that directly calculates the kinetics of enzymatic reactions, without introducing the transition-state theory assumptions, and takes into account the dynamical equilibrium between the reactive and non-reactive conformations of the enzyme/substrate complex. Our computed kcat values are in order-of-magnitude agreement with the experimental data for two representative enzymatic reactions.

Children under 6 years with acute headache in Pediatric Emergency Departments. A 2-year retrospective exploratory multicenter Italian study.

BACKGROUND: Preschool age (i.e. children under six years of age) represents a red flag for requiring neuroimaging to exclude secondary potentially urgent intracranial conditions (PUIC) in patients with acute headache. We investigated the clinical characteristics of preschoolers with headache to identify the features associated with a greater risk of secondary "dangerous" headache. METHODS: We performed a multicenter exploratory retrospective study in Italy from January 2017 to December 2018. Preschoolers with new-onset non-traumatic headache admitted to emergency department were included and were subsequently divided into two groups: hospitalized and discharged. Among hospitalized patients, we investigated the characteristics linked to potentially urgent intracranial conditions. RESULTS: We included 1455 preschoolers with acute headache. Vomiting, ocular motility disorders, ataxia, presence of neurological symptoms and signs, torticollis and nocturnal awakening were significantly associated to hospitalization. Among the 95 hospitalized patients, 34 (2.3%) had potentially urgent intracranial conditions and more frequently they had neurological symptoms and signs, papilledema, ataxia, cranial nerves paralysis, nocturnal awakening and vomiting. Nevertheless, on multivariable logistic regression analysis, we found that only ataxia and vomiting were associated with potentially urgent intracranial conditions. CONCLUSION: Our study identified clinical features that should be carefully evaluated in the emergency department in order to obtain a prompt diagnosis and treatment of potentially urgent intracranial conditions. The prevalence of potentially urgent intracranial conditions was low in the emergency department, which may suggest that age under six should not be considered an important risk factor for malignant causes as previously thought.

Relationship between viral load and symptoms in children infected with SARS-CoV-2.

BACKGROUND: The purpose of this study is to evaluate the association between SARS-CoV-2 viral load in respiratory secretions of infected children and signs/symptoms of COVID-19. METHODS: We reported the clinical characteristics of SARS-CoV-2-infected children during the study period. We compared viral load for several clinical variables, performed a predictive linear regression analysis to identify signs and symptoms significantly associated with viral load, and searched for discriminant viral load thresholds for symptomatic versus asymptomatic infections based on receiver-operating characteristics. RESULTS: A total of 570 patients were included. The median age was 4.75 years. Comparison of CT values by dichotomous variable showed higher viral loads in children with fever, respiratory symptoms, and previous exposure to SARS-CoV-2. The linear regression analysis confirmed a significant relationship between the CT value with these variables and with age, other symptoms, and asymptomaticity. In particular, infants with fever and SARS-CoV-2 exposure had higher viral loads. No viral load cut-offs were found to distinguish symptomatic from asymptomatic patients. CONCLUSION: Our study shows that fever, SARS-CoV-2 exposure, and respiratory symptoms are associated with higher viral load in children, especially infants, while age, presence of nonrespiratory symptoms, or absence of any symptoms are associated with lower viral load. IMPACT: Key message: the clinical variables that best predict viral load in infected children are history of previous exposure to a SARS-CoV-2-infected person and presence of fever and respiratory symptoms (higher viral load). Added value to the current literature: this is the first article to prove this point. IMPACT: SARS-CoV-2 viral load should not be used as a measure of clinical severity of COVID-19 in the pediatric population; however, lower viral load appears to be associated with asymptomatic COVID-19 in older children.

Magnetic-Assisted Capsule Endoscopy in Children With Crohn Disease: Feasibility and Impact on Gastric Transit Time.

OBJECTIVES: Standard capsule endoscopy (CE) is ineffective for upper gastrointestinal (GI) tract examination because it does not allow operator-controlled navigation of the capsule. Magnetically assisted capsule endoscopy (MACE) may offer a solution to these problems. This pilot study is aimed to evaluate the feasibility of MACE system in pediatric Crohn disease (CD) and if magnetic steering could enhance capsule gastric emptying when compared with standard CE. METHODS: Pediatric CD patients already studied by standard small bowel CE were enrolled. All participants swallowed a magnetically assisted CE and an external magnetic field navigator was used to guide the capsule through the upper GI tract. Maneuverability, completeness of the MACE examination, differences in the esophageal transit time (ETT), gastric transit time (GTT), and pyloric transit time (PTT) between standard CE and MACE were assessed. RESULTS: Ten patients [mean age 11.4 years (range 6-15); 60% male] were enrolled. Maneuverability was defined as good and fair in 60% and 40% of participants, respectively. Completeness of MACE examination was 95%, 65%, and 92.5% in the esophagus, proximal, and distal stomach, respectively. Transpyloric passage of the capsule under magnetic control was successfully performed in 80% of patients. Magnetic intervention significantly increased ETT ( P < 0.001) and reduced GTT and PTT ( P = 0.002). No significant adverse events occurred. CONCLUSIONS: MACE is a safe and feasible technique in children. Magnetic steering enhances capsule gastric emptying and facilitates capsule transpyloric passage when compared with standard CE.

Enhanced Sampling Aided Design of Molecular Photoswitches.

Advances in the evolving field of atomistic simulations promise important insights for the design and fundamental understanding of novel molecular photoswitches. Here, we use state-of-the-art enhanced simulation techniques to unravel the complex, multistep chemistry of donor-acceptor Stenhouse adducts (DASAs). Our reaction discovery workflow consists of enhanced sampling for efficient chemical space exploration, refinement of newly observed pathways with more accurate ab initio electronic structure calculations, and structural modifications to introduce design principles within future generations of DASAs. We showcase our discovery workflow by not only recovering the full photoswitching mechanism of DASA but also predicting a plethora of new plausible thermal pathways and suggesting a way for their experimental validation. Furthermore, we illustrate the tunability of these newly discovered reactions, leading to a potential avenue for controlling DASA dynamics through multiple external stimuli. Overall, these insights could offer alternative routes to increase the efficiency and control of DASA's photoswitching mechanism, providing new elements to design more complex light-responsive materials.

Diagnosis of COVID-19 in children guided by lack of fever and exposure to SARS-CoV-2.

BACKGROUND: The objective of this study is to test how certain signs and symptoms related to COVID-19 in children predict the positivity or negativity of the SARS-CoV-2 nasopharyngeal swab in children. METHODS: We review the data of children who were tested for SARS-CoV-2 for a suspected infection. We compared the clinical characteristics of the subjects who tested positive and negative, including the sensibility, positive and negative predictive value of different combination of signs and symptoms. RESULTS: Of all the suspected infected, 2596 tested negative (96.2%) and 103 tested positive (3.8%). The median age was 7.0 and 5.3 years for the positive and negative ones, respectively. The female to male ratio was ~1:1.3. Fever and respiratory symptoms were mostly reported. Most positive children had a prior exposure to SARS-CoV-2-infected subjects (59.2%). A total of 99.3% of patients without fever nor exposure to the virus proved negative to the SARS-CoV-2 test. CONCLUSIONS: Our study suggests that a child without fever or contact with infected subjects is SARS-CoV-2 negative. If this were to be confirmed, many resources would be spared, with improved care of both COVID-19 and not COVID-19-affected children. IMPACT: Key message: lack of fever and exposure to SARS-CoV-2-infected people highly predicts a negative results of the SARS-CoV-2 nasopharyngeal swab in the paediatric population. Added value to the current literature: this is the first article to prove this point. IMPACT: reduction of emergency department accesses of children with suspected SARS-CoV-2 infection; increased outpatient management of children with cough or other common respiratory symptoms of infancy; sparing of many human and material health resources.

Bringing chemical structures to life with augmented reality, machine learning, and quantum chemistry.

Visualizing 3D molecular structures is crucial to understanding and predicting their chemical behavior. However, static 2D hand-drawn skeletal structures remain the preferred method of chemical communication. Here, we combine cutting-edge technologies in augmented reality (AR), machine learning, and computational chemistry to develop MolAR, an open-source mobile application for visualizing molecules in AR directly from their hand-drawn chemical structures. Users can also visualize any molecule or protein directly from its name or protein data bank ID and compute chemical properties in real time via quantum chemistry cloud computing. MolAR provides an easily accessible platform for the scientific community to visualize and interact with 3D molecular structures in an immersive and engaging way.

Children With a Soft Scalp Hematoma Presenting to the Emergency Department More Than 24 Hours After a Head Injury.

OBJECTIVES: The soft scalp hematoma is one of the clinical markers used as a predictor for the presence of intracranial injury in children with a head trauma. We evaluated the significance of time presentation in the management of these patients. METHODS: We conducted a retrospective study of children and adolescents aged 0 to <18 years by comparing the clinical, radiological, and epidemiological features in those presenting within 24 hours with those presenting greater than 24 hours after a head injury. RESULTS: We identified 188 and 98 patients with early presentation and late presentation, respectively. The percentage of children aged 0 to <6 months was lower in those with late presentation (6.12%) than those with early presentation (20.21%) with a significant difference (P < .001). Likewise, the percentage of children aged ≥24 months was lower in children with late presentation (7.14%) than those with early presentation (34.04%) with a significant difference (P < .001). The severe mechanism rate was more elevated in early presentation (38.83%) with a significant difference (-14.34%; 95% confidence interval [CI], -25.34% to -3.34%; P = .015). The symptom rate resulted higher in early presentation (14.36%) with a significant difference (-11.30%; 95% CI, -17.36% to 5.22%; P = .003). The parietal scalp hematoma occurred mostly in children with late presentation (85.71%) with a significant difference (19.76%; 95% CI, 10.07% to 29.45%; P < .001). The occipital scalp hematoma rate was higher in early presentation with a significant difference (-17.50%; 95% CI, -22.99% to -12.12%; P < .001). There was no significant difference in the prevalence of different types of intracranial injury, and the only 5 patients needing a neurosurgical intervention were exclusively children with an early presentation. CONCLUSION: Although children with soft scalp hematoma presenting to the emergency department greater than 24 hours after a head injury may have pathological findings on computed tomography, all of them had a good short- and long-term outcomes, and no neurological deterioration aroused the medical attention on follow-up. For this subset of patients that does not experience red flags (neurological symptoms, focal signs on examination, or severe injury mechanism), a wait-and-see approach might be more appropriate rather than neuroimaging.

Hypoglycemia in a Pediatric Emergency Department: Single-Center Experience on 402 Children.

OBJECTIVES: This study aimed to establish the rate, etiology, and short-term outcome of hypoglycemia in infants and children accessing an emergency department of a tertiary care pediatric hospital. METHODS: The study was retrospectively conducted on the clinical records of children with hypoglycemia aged 15 days to 17 years who were admitted consecutively to the emergency department during a 6-year period for various clinical conditions. Hypoglycemia was defined as a venous plasma glucose level lower than 45 mg/dL. RESULTS: Hypoglycemia was detected in 402 patients (female-to-male ratio, 1.26; mean age, 2.6 ± 1.8 years), with a rate of 0.99 per 1000 children. Plasma glucose levels ranged from 3 to 45 (mean, 37.48 ± 7.44) mg/dL. Hypoglycemia was associated with gastroenteritis or other infectious diseases causing protracted fasting in 86.32% of cases, whereas hypoglycemia related to a different etiology (HDE) was observed in 13.68% of hypoglycemic children. Most HDE patients had a final diagnosis of ketotic hypoglycemia, whereas metabolic defects were a rare (1.49%) but nonnegligible etiologic cause. A severe triage code was more frequent in the HDE group (P < 0.001). Factors significantly and independently associated with HDE were impaired level of consciousness, assessed with the AVPU scale (A, alert; V, responding to verbal; P, responding to pain; U, unresponsive; adjusted odds ratio, 2.50; P = 0.025) and clinical onset within 12 hours (adjusted odds ratio, 3.98; P < 0.001). CONCLUSIONS: In a nonnegligible number of critically ill children, hypoglycemia can be detected. In a minority of cases, hypoglycemia was due to metabolic disorders that should be suspected on the basis of the severity of hypoglycemia, and the recent onset and the presence of neuroglycopenic symptoms.

Hematemesis in Infants: The First Evidence-Based Score to Predict the Need for Timely Endoscopy.

OBJECTIVES: Infantile acute upper gastrointestinal bleeding involves a decision for therapeutic intervention that most pediatricians first coming into contact with the patient are, not unreasonably, unable to objectively provide. Therefore, some objective tools of individual risk assessment would seem to be crucial. The principal aim of the present study was to investigate the anamnestic and clinical parameters of infants with hematemesis, together with laboratory and instrumental findings, to create a scoring system that may help identify those infants requiring an appropriate and timely application of upper gastrointestinal (GI) endoscopy. METHODS: Clinical data of infants admitted for hematemesis to the participating centers over the study period were systematically collected. According to the outcome dealing with rebleeding, need for blood transfusion, mortality, finding of GI bleeding lesions, or need for surgical intervention, patients were blindly divided into a group with major clinical severity and a group with minor clinical severity. Univariate and multivariate logistic regressions were conducted to investigate significant prognostic factors for clinical severity. RESULTS: According to our findings, we drafted a practical diagnostic algorithm and a clinical score able to predict the need for timely upper GI endoscopy (BLOVO infant score). Our clinical scoring system was created by incorporating anamnestic factors, clinical parameters, and laboratory findings that emerged as predictors of a worst outcome. CONCLUSIONS: We provided the first objective tool of individual risk assessment for infants with hematemesis, which could be very useful for pediatricians first coming into contact with the patient in the emergency department.

Early echocardiographic evaluation of children admitted to the emergency department for anorexia nervosa during the COVID-19 pandemic.

PURPOSE: Anorexia nervosa (AN) is the most frequent eating disorder (ED), whose cardiac complications may have life-threatening consequences for both the physical and psychological health of affected children. In this study, we reported and analysed the echocardiographic anomalies found in pediatric patients diagnosed with AN. METHODS: We reported the demographic and clinical characteristics of children aged 8 to 18 years, who were diagnosed with AN and underwent a complete cardiological evaluation at the Emergency Department of the Bambino Gesù Children's Hospital, IRCCS, Rome between the 1st January 2021 and the 30th June 2021. Furthermore, we compared the patients according to the presence of pericardial effusion and a BMI (body mass index) cut-off 14.5 kg/m2. RESULTS: Forty-nine patients were included in the study. The mean age was 15.1 years. Most patients were female (89.8%). The mean length of hospitalization was 18 days. The mean BMI at admission was 14.8 kg/m2, with a median weight loss of 9 kg in the last year. Eleven patients (22.4%) presented with cardiovascular signs or symptoms at admission. Most patients had pericardial effusion on heart ultrasound, with a mean thickness of 6 mm (SD ± 4). The LV (left ventricle) thickness over age was significantly higher in patients with pericardial effusion, with a Z score of -2.0 vs -1.4 (p = 0.014). The administration of psychiatric drugs was significantly more frequent in patients with a lower BMI (37.5% vs 12%, p = 0.038). CONCLUSION: Our study suggests that a non-urgent baseline echocardiographic evaluation with focus on left-ventricular wall thickness and mass in children with anorexia nervosa is advisable. LEVEL III: Evidence obtained from cohort or case-control analytic studies.

Psychiatric comorbidities and dehydration are more common in children admitted to the emergency department for eating disorders in the COVID-19 era.

PURPOSE: Since the beginning of COVID-19 pandemic, social distancing and home confinement had a significant impact on children, especially on those with eating disorders (ED). The primary objective of this retrospective study was to describe and analyze the demographic and clinical profiles of children presenting with ED during the COVID-19 pandemic. METHODS: We conducted a retrospective review of clinical charts of patients with ED younger than 18 years who accessed the emergency department of the Bambino Gesù Children's Hospital, Rome, between March 2019 and March 2021. Of these, we reported and compared the demographic, clinical and laboratory data before and after the COVID-19 pandemic and looked for predictors of ED severity. RESULTS: A total of 211 admissions for ED were recorded. The patients, mostly females (86.3%) were on average 14.1 years old. The mean weight loss on admission was 11 kg. Bradycardia was observed in 31.3% of the study sample. 16.6% of patients had an associated psychiatric disorder and 60.2% required psychotropic drugs. 68.7% of the patients required hospitalization. Respectively, 96 and 115 patients were admitted before and during the COVID-19 pandemic. The latter were hospitalized more (78.3 vs 57.3%; p = 0.001), yet for less time (19 vs 26 days; p = 0.004), had a higher mean serum creatinine (0.68 vs 0.47; p < 0.001) and were more frequently diagnosed with an associated psychiatric disorder (23.5 vs 8.3%; p = 0.003). CONCLUSION: Our study shows a significant increase of hospitalizations of children with ED during the COVID-19 pandemic, along with a shorter length of stay, more psychiatric comorbidities, and some distinctive features at the laboratory work-up, such as an increase of serum creatinine and/or a reduction of serum albumin. LEVEL OF EVIDENCE: III, evidence obtained from well-designed cohort or case-control analytic studies.

In Silico Discovery of Multistep Chemistry Initiated by a Conical Intersection: The Challenging Case of Donor-Acceptor Stenhouse Adducts.

Detailed mechanistic understanding of multistep chemical reactions triggered by internal conversion via a conical intersection is a challenging task that emphasizes limitations in theoretical and experimental techniques. We present a discovery-based, hypothesis-free computational approach based on first-principles molecular dynamics to discover and refine the switching mechanism of donor-acceptor Stenhouse adducts (DASAs). We simulate the photochemical experiment in silico, following the "hot" ground state dynamics for 10 ps after photoexcitation. Using state-of-the-art graphical processing units-enabled electronic structure calculations we performed in total ∼2 ns of nonadiabatic ab initio molecular dynamics discovering (a) critical intermediates that are involved in the open-to-closed transformation, (b) several competing pathways which lower the overall switching yield, and (c) key elements for future design strategies. Our dynamics describe the natural evolution of both the nuclear and electronic degrees of freedom that govern the interconversion between DASA ground-state intermediates, exposing significant elements for future design strategies of molecular switches.

A combined Monte Carlo/DFT approach to simulate UV-vis spectra of molecules and aggregates: Merocyanine dyes as a case study.

The combination of a Monte Carlo (MC) sampling of the configurational space with time dependent-density functional theory (TD-DFT) to estimate vertical excitations energies has been applied to compute the absorption spectra of a family of merocyanine dyes in both their monomeric and dimeric forms. These results have been compared to those obtained using a static DFT/TD-DFT approach as well as to the available experimental spectra. Though suffering of the limitations related to the use of DFT and TD-DFT for this type of systems, our data clearly show that the classical MC sampling provides a suitable alternative to classical molecular dynamics to explore the structural flexibility of these donor-acceptor (D-π-A) chromophores enabling a realistic description of the potential energy surface of both their monomers and aggregates (here dimers) and thus of their spectra. Overall, the combination of MC sampling with quantum mechanics (TD-DFT) calculations, carried out in implicit dioxane solvent on random snapshots, provides a workable compromise to solve the combined challenge of accuracy and time-consuming problem not only for merocyanines momers, but also for their dimers, up to now less investigated. Indeed, the simulated absorption spectra fairly agree with the experimental ones, suggesting the general reliability of the method.

Water-Mediated Excited State Proton Transfer of Pyranine-Acetate in Aqueous Solution: Vibrational Fingerprints from Ab Initio Molecular Dynamics.

In this work, we simulate the excited state proton transfer (ESPT) reaction involving the pyranine photoacid and an acetate molecule as proton acceptor, connected by a bridge water molecule. We employ ab initio molecular dynamics combined with an hybrid quantum/molecular mechanics (QM/MM) framework. Furthermore, a time-resolved vibrational analysis based on the wavelet-transform allows one to identify two low frequency vibrational modes that are fingerprints of the ESPT event: a ring wagging and ring breathing. Their composition suggests their key role in optimizing the structure of the proton donor-acceptor couple and promoting the ESPT event. We find that the choice of the QM/MM partition dramatically affects the photoinduced reactivity of the system. The QM subspace was gradually extended including the water molecules directly interacting with the pyranine-water-acetate system. Indeed, the ESPT reaction takes place when the hydrogen bond network around the reactive system is taken into account at full QM level.

Consensus statements on the information to deliver after a febrile seizure.

Febrile seizures (FS) are usually self-limiting and cause no morbidity. Nevertheless they represent very traumatic events for families. There is a need to identify key messages that reassure carers and help to prevent inappropriate, anxiety-driven behaviors associated with "fever phobia." No recommendations have been proposed to date regarding the content of such messages. Using a Delphi process, we have established a consensus regarding the information to be shared with families following a FS. Twenty physicians (child neurologists and pediatricians) from five European countries participated in a three-step Delphi process between May 2018 and October 2019. In the first step, each expert was asked to give 10 to 15 free statements about FS. In the second and third steps, statements were scored and selected according to the expert ranking of importance. A list of key messages for families has emerged from this process, which offer reassurance about FS based on epidemiology, underlying mechanisms, and the emergency management of FS should they recur. Interestingly, there was a high level of agreement between child neurologists and general pediatricians.Conclusion: We propose key messages to be communicated with families in the post-FS clinic setting. What is Known: • Febrile seizures (FS) are traumatic events for families. • No guidelines exist on what information to share with parents following a FS. What is New: • A Delphi process involving child neurologists and pediatricians provides consensual statement about information to deliver after a febrile seizure. • We propose key messages to be communicated with families in the post-FS clinic setting.

Uncommon Presentation of Childhood Leukemia in Emergency Department: The Usefulness of an Early Multidisciplinary Approach.

ABSTRACT: Leukemia is the most common childhood malignancy, and it is often characterized by pallor, fatigue, cytopenia, and organomegaly; sometimes musculoskeletal symptoms, mainly characterized by diffuse bone pain in the lower extremities, are the onset clinical characteristics of the disease. In these cases, the disease may initially be misdiagnosed as reactive arthritis, osteomyelitis, or juvenile idiopathic arthritis delaying appropriate diagnosis and management. Even if leukopenia, thrombocytopenia, and a history of nighttime pain are reported to be the most important predictive factors for a pediatric leukemia, blood examinations can sometimes be subtle or within normal limits, and this represents a further diagnostic difficulty. Radiological findings of leukemic bone involvement are described in patients with musculoskeletal symptoms of acute lymphoblastic leukemia and often appear before hematologic anomalies, but they are not specific for the disease. However, they could be helpful to get the right diagnosis if integrated with other features; thus, it is important knowing them, and it is mandatory for the multidisciplinary comparison to talk about dubious cases even in an emergency setting. We describe 4 patients visited in the emergency department for musculoskeletal complaints and having radiological lesions and a final diagnosis of acute lymphoblastic leukemia, in whom the onset of the manifestations could mimic orthopedic/rheumatologic diseases.

Ab-initio molecular dynamics and hybrid explicit-implicit solvation model for aqueous and nonaqueous solvents: GFP chromophore in water and methanol solution as case study.

Solute-solvent interactions are proxies for understanding how the electronic density of a chromophore interacts with the environment in a more exhaustive way. The subtle balance between polarization, electrostatic, and non-bonded interactions need to be accurately described to obtain good agreement between simulations and experiments. First principles approaches providing accurate configurational sampling through molecular dynamics may be a suitable choice to describe solvent effects on solute chemical-physical properties and spectroscopic features, such as optical absorption of dyes. In this context, accurate energy potentials, obtained by hybrid implicit/explicit solvation methods along with employing nonperiodic boundary conditions, are required to represent bulk solvent around a large solute-solvent cluster. In this work, a novel strategy to simulate methanol solutions is proposed combining ab initio molecular dynamics, a hybrid implicit/explicit flexible solvent model, nonperiodic boundary conditions, and time dependent density functional theory. As case study, the robustness of the proposed protocol has been gauged by investigating the microsolvation and electronic absorption of the anionic green fluorescent protein chromophore in methanol and aqueous solution. Satisfactory results are obtained, reproducing the microsolvation layout of the chromophore and, as a consequence, the experimental trends shown by the optical absorption in different solvents.