ArticleFaraday discussions2024
Harnessing conformational dynamics in enzyme catalysis to achieve nature-like catalytic efficiencies: the shortest path map tool for computational enzyme redesign.
Article in Faraday discussions, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 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
6 citing papers in PubMed.
- How far can you go? Extrapolating values of catalytic activity from known protein landscapes in natural and directed evolution.Chemical Society reviews · 2026Review
- Decoding the substrate specificity landscape of a promiscuous enzyme through multi-substrate mutational scanning.Nature communications · 2026Article
- Identification and understanding of allostery hotspots in proteins: Integration of deep mutational scanning and multi-faceted computational analyses.Journal of molecular biology · 2025Review
- Approaches for regulating enzyme activities: Recent advances in experiment and computation.Current opinion in structural biology · 2025Review
- Deciphering opening mechanisms of 14-3-3 proteins.Protein science : a publication of the Protein Society · 2025Article
- Physics-based modeling in the new era of enzyme engineering.Nature computational science · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Enzymes exhibit diverse conformations, as represented in the free energy landscape (FEL). Such conformational diversity provides enzymes with the ability to evolve towards novel functions. The challenge lies in identifying mutations that enhance specific conformational changes, especially if located in distal sites from the active site cavity. The shortest path map (SPM) method, which we developed to address this challenge, constructs a graph based on the distances and correlated motions of residues observed in nanosecond timescale molecular dynamics (MD) simulations. We recently introduced a template based AlphaFold2 (tAF2) approach coupled with 10 nanosecond MD simulations to quickly estimate the conformational landscape of enzymes and assess how the FEL is shifted after mutation. In this study, we evaluate the potential of SPM when coupled with tAF2-MD in estimating conformational heterogeneity and identifying key conformationally-relevant positions. The selected model system is the beta subunit of tryptophan synthase (TrpB). We compare how the SPM pathways differ when integrating tAF2 with different MD simulation lengths from as short as 10 ns until 50 ns and considering two distinct Amber forcefield and water models (ff14SB/TIP3P
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.