A5102822851- RNA and protein synthesis mechanisms
- Receptor Mechanisms and Signaling
- DNA and Biological Computing
- thermodynamics and calorimetric analyses
- Chemical Synthesis and Analysis
- Neuroscience and Neuropharmacology Research
- Computational Drug Discovery Methods
- DNA and Nucleic Acid Chemistry
- RNA modifications and cancer
- Photoreceptor and optogenetics research
- Protein Structure and Dynamics
- Bacterial Genetics and Biotechnology
- Neurotransmitter Receptor Influence on Behavior
- Bacteriophages and microbial interactions
- Machine Learning in Materials Science
- Radiopharmaceutical Chemistry and Applications
- Click Chemistry and Applications
Schrodinger (United States)
2022-2025
National Institute on Drug Abuse
2023
Abstract As genetic code expansion advances beyond l -α-amino acids to backbone modifications and new polymerization chemistries, delineating what substrates the ribosome can accommodate remains a challenge. The Escherichia coli tolerates non- in vitro, but few structural insights that explain how are available, boundary conditions for efficient bond formation so far unknown. Here we determine high-resolution cryogenic electron microscopy structure of E. containing α-amino acid monomers use...
The programmed synthesis of sequence-defined biomaterials whose monomer backbones diverge from those canonical α-amino acids represents the next frontier in protein and biomaterial evolution. Such next-generation molecules provide otherwise nonexistent opportunities to develop improved biologic therapies, bioremediation tools, biodegradable plastic-like materials. One family particular interest for includes β-hydroxy acids. Many natural products contain isolated acid monomers, polymers...
Accurate prediction of the affinity ligand binding to nucleic acids represents a formidable challenge for current computational approaches. This limitation has hindered use methods develop small-molecule drugs that modulate activity acids, including those associated with anticancer, antiviral, and antibacterial effects. In recent years, significant scientific technological advances as well easier access compute resources have contributed free-energy perturbation (FEP) becoming one most...
Ribonucleic acids (RNAs) are emerging as important drug targets, yet in silico modeling of RNA-small molecule interactions presents unique challenges compared to protein targets. This study evaluates and improves computational tools within the Schrödinger Suite for hit discovery against RNA. We benchmarked enhanced SiteMap identifying RNA binding sites, introducing an RNA-specific scoring function that improved site prediction accuracy from 44.4% 65.3% on a filtered HARIBOSS dataset. also...
Ribonucleic acids (RNAs) are emerging as important drug targets, yet in silico modeling of RNA-small molecule interactions presents unique challenges compared to protein targets. This study evaluates and improves computational tools within the Schrödinger Suite for hit discovery against RNA. We benchmarked enhanced SiteMap identifying RNA binding sites, introducing an RNA-specific scoring function that improved site prediction accuracy from 44.4% 65.3% on a filtered HARIBOSS dataset. also...
The serotonin transporter (SERT) tightly regulates synaptic levels and has been the primary target of antidepressants. Binding inhibitors to allosteric site human SERT (hSERT) impedes dissociation antidepressants bound at central may enhance efficacy such potentially reduce their dosage side effects. Here, we report identification a series high-affinity hSERT in unique scaffold, with lead compound, Lu AF88273 (3-(1-(2-(1
Abstract Synthesis of sequence-defined biomaterials whose monomer backbones diverge from canonical α-amino acids represents the next frontier in protein and biomaterial evolution with potential to yield better biological therapeutics, bioremediation tools, biodegradable plastic-like materials. One family particular interest for are β-hydroxy acids. Many natural products contain isolated β-esters, polymeric β-esters found polyhydroxyalkanoate (PHA) polyesters under development as bioplastics...
Abstract As genetic code expansion advances beyond L-α-amino acids to backbone modifications and new polymerization chemistries, the field faces an increasingly broad challenge discover what ribosome can accommodate. Although E. coli tolerates non-L-α-amino in vitro , few structural insights are available, boundary conditions for efficient bond formation unknown. We describe a 2.1 Å cryo-EM structure of containing well-resolved α-amino acid monomers coupled with computational approach which...
The serotonin transporter (SERT) tightly regulates synaptic levels and has been the primary target of antidepressants. Binding inhibitors to allosteric site human SERT (hSERT) impedes dissociation antidepressants bound at central site, may enhance efficacy such potentially reduce their dosage side effects. Here we report discovery a series high-affinity hSERT in novel scaffold, with lead compound, Lu AF88273 (3-(1-(2-(1H-indol-3-yl)ethyl)piperidin-4-yl)-6-chloro-1H-indole), having 2.1 nM...
Accurate prediction of the affinity ligand binding to nucleic acids represents a significant challenge for current computational approaches. This limitation has hindered use methods develop small molecule drugs that modulate activity acids, including those associated with anticancer, antiviral and antibacterial effects. In recent years, scientific technological advances as well easier access compute resources have contributed free-energy perturbation (FEP) becoming one most consistently...