What indeed can GPT models do in chemistry? A comprehensive benchmark on eight tasks

Large Language Models (LLMs) with strong abilities in natural language processing tasks have emerged and have been rapidly applied in various kinds of areas such as science, finance and software engineering. However, the capability of LLMs to advance the field of chemistry remains unclear. In this paper,we establish a comprehensive benchmark containing 8 practical chemistry tasks, including 1) name prediction, 2) property prediction, 3) yield prediction, 4) reaction prediction, 5) retrosynthesis (prediction of reactants from products), 6)text-based molecule design, 7) molecule captioning, and 8) reagent selection. Our analysis draws on widely recognized datasets including BBBP, Tox21, PubChem, USPTO, and ChEBI, facilitating a broad exploration of the capacities of LLMs within the context of practical chemistry. Three GPT models (GPT-4, GPT-3.5,and Davinci-003) are evaluated for each chemistry task in zero-shot and few-shot in-context learning settings with carefully selected demonstration examples and specially crafted prompts. The key results of our investigation are 1) GPT-4 outperforms the other two models among the three evaluated; 2) GPT models exhibit less competitive performance in tasks demanding precise understanding of molecular SMILES representation, such as reaction prediction and retrosynthesis;3) GPT models demonstrate strong capabilities in text-related explanation tasks such as molecule captioning; and 4) GPT models exhibit comparable or better performance to classical machine learning models when applied to chemical problems that can be transformed into classification or ranking tasks, such as property prediction, and yield prediction

Relative reactivity of alkenyl alcohols in the palladium-catalyzed redox-relay Heck reaction

The relative rates of alkenyl alcohols in the Pd-catalyzed redox-relay Heck reaction were measured in order to examine the effect of their steric and electronic properties on the rate-determining step. Competition experiments between an allylic alkenyl alcohol and two substrates with differing chain lengths revealed that the allylic alcohol reacts 3–4 times faster in either case. Competition between di- and trisubstituted alkenyl alcohols provided an interesting scenario, in which the disubstituted alkene was consumed first followed by reaction of the trisubstituted alkene. Consistent with this observation, the transition structures for the migratory insertion of the aryl group into the di- and trisubstituted alkenes were calculated with a lower barrier for the former. An internal competition between a substrate containing two alcohols with differing chain lengths demonstrated the catalyst's preference for migrating toward the closest alcohol. Additionally, it was observed that increasing the electron-density in the arene boronic acid promotes a faster reaction, which correlates with Hammett [sigma-rho] values to give a [rho] of −0.87

German Ageing Survey (DEAS) - the second half of life: research instruments of the third wave

Contents: 1. Introduction; 2. Main research areas; 3. Sampling; 4. Survey methods; 5. Project management and staff; 6. Data access; 7. Survey documents

German Ageing Survey (DEAS) - the second half of life: research instruments of the third wave

Contents: 1. Introduction; 2. Main research areas; 3. Sampling; 4. Survey methods; 5. Project management and staff; 6. Data access; 7. Survey documents

Graph-based Molecular Representation Learning

Molecular representation learning (MRL) is a key step to build the connection between machine learning and chemical science. In particular, it encodes molecules as numerical vectors preserving the molecular structures and features, on top of which the downstream tasks (e.g., property prediction) can be performed. Recently, MRL has achieved considerable progress, especially in methods based on deep molecular graph learning. In this survey, we systematically review these graph-based molecular representation techniques, especially the methods incorporating chemical domain knowledge. Specifically, we first introduce the features of 2D and 3D molecular graphs. Then we summarize and categorize MRL methods into three groups based on their input. Furthermore, we discuss some typical chemical applications supported by MRL. To facilitate studies in this fast-developing area, we also list the benchmarks and commonly used datasets in the paper. Finally, we share our thoughts on future research directions

HSP90 inhibitors reduce cholesterol storage in Niemann-Pick type C1 mutant fibroblasts

Niemann Pick type C1 (NPC1) disease is a lysosomal lipid storage disorder caused by mutations of the NPC1 gene. More than 300 disease-associated mutations are reported in patients, resulting in abnormal accumulation of unesterified cholesterol, glycosphingolipids and other lipids in late endosomes and lysosomes (LE/Ly) of many cell types. Previously, we showed that treatment of many different NPC1 mutant fibroblasts with histone deacetylase inhibitors resulted in reduction of cholesterol storage, and we found that this was associated with enhanced exit of the NPC1 protein from the endoplasmic reticulum and delivery to LE/Ly. This suggested that histone deacetylase inhibitors may work through changes in protein chaperones to enhance the folding of NPC1 mutants, allowing them to be delivered to LE/Ly. In this study we evaluated the effect of several HSP90 inhibitors on NPC

Deutscher Alterssurvey - die zweite Lebenshälfte: Erhebungsdesign und Instrumente der dritten Befragungswelle

Der Deutsche Alterssurvey (DEAS) ist eine bundesweit repräsentative Quer- und Längsschnittbefragung von Personen, die sich in der zweiten Lebenshälfte befinden, und wird aus Mitteln des Bundesministeriums für Familie, Senioren, Frauen und Jugend (BMFSFJ) gefördert. Die umfassende Untersuchung von Personen im mittleren und höheren Erwachsenenalter dient dazu, Mikrodaten bereitzustellen, die sowohl für die sozial- und verhaltenswissenschaftliche Forschung als auch für die Sozialberichterstattung genutzt werden. Die DEAS-Daten bilden damit eine Informationsgrundlage für politische Entscheidungsträger, die interessierte Öffentlichkeit und für die wissenschaftliche Forschung. Die erste Welle wurde im Jahr 1996 durchgeführt, die zweite Welle im Jahr 2002. Die aktuelle dritte Welle wurde im Jahr 2008 verwirklicht. Wie bereits in den vorangegangenen Erhebungswellen wurden auch in der dritten Welle Personen umfassend zu ihrer Lebenssituation befragt - unter anderem zu ihrem beruflichen Status oder ihrem Leben im Ruhestand, zu gesellschaftlicher Partizipation und nachberuflichen Aktivitäten, wirtschaftlicher Lage und Wohnsituation, familiären und außerfamiliären sozialen Beziehungen sowie zu Gesundheit, Wohlbefinden und Lebenszielen. Der vorliegende Beitrag gibt einen kurzen Überblick über die Befragungsschwerpunkte, die Stichproben, die Befragungsmethoden, die beteiligten Personen, die Nutzung der Daten und die Erhebungsunterlagen. (ICI2). Inhaltsverzeichnis: 1. Einleitung; 2. Befragungsschwerpunkte; 3. Stichproben; 4. Befragungsmethoden; 5. Beteiligte Personen und Kontakt; 6. Nutzung der Daten; 7. Erhebungsunterlagen

Deutscher Alterssurvey - die zweite Lebenshälfte: Erhebungsdesign und Instrumente der dritten Befragungswelle

Der Deutsche Alterssurvey (DEAS) ist eine bundesweit repräsentative Quer- und Längsschnittbefragung von Personen, die sich in der zweiten Lebenshälfte befinden, und wird aus Mitteln des Bundesministeriums für Familie, Senioren, Frauen und Jugend (BMFSFJ) gefördert. Die umfassende Untersuchung von Personen im mittleren und höheren Erwachsenenalter dient dazu, Mikrodaten bereitzustellen, die sowohl für die sozial- und verhaltenswissenschaftliche Forschung als auch für die Sozialberichterstattung genutzt werden. Die DEAS-Daten bilden damit eine Informationsgrundlage für politische Entscheidungsträger, die interessierte Öffentlichkeit und für die wissenschaftliche Forschung. Die erste Welle wurde im Jahr 1996 durchgeführt, die zweite Welle im Jahr 2002. Die aktuelle dritte Welle wurde im Jahr 2008 verwirklicht. Wie bereits in den vorangegangenen Erhebungswellen wurden auch in der dritten Welle Personen umfassend zu ihrer Lebenssituation befragt - unter anderem zu ihrem beruflichen Status oder ihrem Leben im Ruhestand, zu gesellschaftlicher Partizipation und nachberuflichen Aktivitäten, wirtschaftlicher Lage und Wohnsituation, familiären und außerfamiliären sozialen Beziehungen sowie zu Gesundheit, Wohlbefinden und Lebenszielen. Der vorliegende Beitrag gibt einen kurzen Überblick über die Befragungsschwerpunkte, die Stichproben, die Befragungsmethoden, die beteiligten Personen, die Nutzung der Daten und die Erhebungsunterlagen. (ICI2). Inhaltsverzeichnis: 1. Einleitung; 2. Befragungsschwerpunkte; 3. Stichproben; 4. Befragungsmethoden; 5. Beteiligte Personen und Kontakt; 6. Nutzung der Daten; 7. Erhebungsunterlagen

A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria

Artemisinins are the cornerstone of anti-malarial drugs. Emergence and spread of resistance to them raises risk of wiping out recent gains achieved in reducing worldwide malaria burden and threatens future malaria control and elimination on a global level. Genome-wide association studies (GWAS) have revealed parasite genetic loci associated with artemisinin resistance. However, there is no consensus on biochemical targets of artemisinin. Whether and how these targets interact with genes identified by GWAS, remains unknown. Here we provide biochemical and cellular evidence that artemisinins are potent inhibitors of Plasmodium falciparum phosphatidylinositol-3-kinase (PfPI3K), revealing an unexpected mechanism of action. In resistant clinical strains, increased PfPI3K was associated with the C580Y mutation in P. falciparum Kelch13 (PfKelch13), a primary marker of artemisinin resistance. Polyubiquitination of PfPI3K and its binding to PfKelch13 were reduced by the PfKelch13 mutation, which limited proteolysis of PfPI3K and thus increased levels of the kinase, as well as its lipid product phosphatidylinositol-3-phosphate (PI3P). We find PI3P levels to be predictive of artemisinin resistance in both clinical and engineered laboratory parasites as well as across non-isogenic strains. Elevated PI3P induced artemisinin resistance in absence of PfKelch13 mutations, but remained responsive to regulation by PfKelch13. Evidence is presented for PI3P-dependent signalling in which transgenic expression of an additional kinase confers resistance. Together these data present PI3P as the key mediator of artemisinin resistance and the sole PfPI3K as an important target for malaria elimination

Identifying Ligand Binding Conformations of the β2-Adrenergic Receptor by Using Its Agonists as Computational Probes

Recently available G-protein coupled receptor (GPCR) structures and biophysical studies suggest that the difference between the effects of various agonists and antagonists cannot be explained by single structures alone, but rather that the conformational ensembles of the proteins need to be considered. Here we use an elastic network model-guided molecular dynamics simulation protocol to generate an ensemble of conformers of a prototypical GPCR, β2-adrenergic receptor (β2AR). The resulting conformers are clustered into groups based on the conformations of the ligand binding site, and distinct conformers from each group are assessed for their binding to known agonists of β2AR. We show that the select ligands bind preferentially to different predicted conformers of β2AR, and identify a role of β2AR extracellular region as an allosteric binding site for larger drugs such as salmeterol. Thus, drugs and ligands can be used as "computational probes" to systematically identify protein conformers with likely biological significance. © 2012 Isin et al