ArticleThe journal of physical chemistry letters2019
Overcoming Challenging Substituent Perturbations with Multisite λ-Dynamics: A Case Study Targeting β-Secretase 1.
Article in The journal of physical chemistry letters, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed.
- Determination of coverage-dependent surface reaction rates using λ-dynamics: Application to molecular desorption.The journal of physical chemistry. C, Nanomaterials and interfaces · 2026Article
- Accurate in silico predictions of modified RNA interactions to a prototypical RNA-binding protein with λ-dynamics.RNA (New York, N.Y.) · 2025Article
- Simultaneous Construction of Free Energy Surfaces via Multisite λ Dynamics and Umbrella Sampling.Journal of chemical theory and computation · 2025Article
- Multiple Molecule λ-Dynamics: Probing Drug Resistance with Concurrent Protein and Ligand Perturbations.The journal of physical chemistry letters · 2025Article
- Relative Binding Free Energy Estimation of Congeneric Ligands and Macromolecular Mutants with the Alchemical Transfer Method with Coordinate Swapping.Journal of chemical information and modeling · 2025Article
- In silico λ-dynamics predicts protein binding specificities to modified RNAs.Nucleic acids research · 2025Article
- Superimposing Ligands with a Ligand Overlay as an Alternate Topology Model for λ-Dynamics-Based Calculations.The journal of physical chemistry. B · 2024Article
- CHARMM at 45: Enhancements in Accessibility, Functionality, and Speed.The journal of physical chemistry. B · 2024Review
- How to Sample Dozens of Substitutions per Site with λ Dynamics.Journal of chemical theory and computation · 2024Article
- A λ-Dynamics Investigation of InsulinJournal of chemical information and modeling · 2024Article
- A λ-dynamics investigation of insulinbioRxiv : the preprint server for biology · 2024Article
- Investigating Polypharmacology through Targeting Known Human Neutrophil Elastase Inhibitors to Proteinase 3.Journal of chemical information and modeling · 2024Article
- In silico λ-dynamics predicts protein binding specificities to modified RNAs.bioRxiv : the preprint server for biology · 2024Article
- Fast free energy estimates from λ-dynamics with bias-updated Gibbs sampling.Nature communications · 2023Article
- QSAR via multisite λ-dynamics in the orphaned TSSK1B kinase.Protein science : a publication of the Protein Society · 2023Article
- An Empirical Quantitative Structure-Activity Relationship Equation Assists the Discovery of High-Affinity Phosphodiesterase 4D Inhibitors as Leads to PET Radioligands.Journal of medicinal chemistry · 2023Article
- Addressing Intersite Coupling Unlocks Large Combinatorial Chemical Spaces for Alchemical Free Energy Methods.Journal of chemical theory and computation · 2022Article
- Alchemical Free Energy Methods Applied to Complexes of the First Bromodomain of BRD4.Journal of chemical information and modeling · 2022Article
- Optimizing Multisite λ-Dynamics Throughput with Charge Renormalization.Journal of chemical information and modeling · 2022Article
- BLaDE: A Basic Lambda Dynamics Engine for GPU-Accelerated Molecular Dynamics Free Energy Calculations.Journal of chemical theory and computation · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Alchemical free energy calculations have made a dramatic impact upon the field of structure-based drug design by allowing functional group modifications to be explored computationally prior to experimental synthesis and assay evaluation, thereby informing and directing synthetic strategies. In furthering the advancement of this area, a series of 21 β-secretase 1 (BACE1) inhibitors developed by Janssen Pharmaceuticals were examined to evaluate the ability to explore large substituent perturbations, some of which contain scaffold modifications, with multisite λ-dynamics (MSλD), an innovative alchemical free energy framework. Our findings indicate that MSλD is able to efficiently explore all structurally diverse ligand end-states
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.