ArticleBiochemistry2013
Connecting protein conformational dynamics with catalytic function as illustrated in dihydrofolate reductase.
Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed.
- Machine Learning Quantum Mechanical/Molecular Mechanical Potentials: Evaluating Transferability in Dihydrofolate Reductase-Catalyzed Reactions.Journal of chemical theory and computation · 2025Article
- Engineering Protein Dynamics through Mutational Energy Landscape Traps.Journal of chemical information and modeling · 2025Article
- Method and Implementation of Projected Hybrid Orbitals for Treating Multiple Covalent Bonds in Combined QM/MM Calculations.Journal of chemical theory and computation · 2024Article
- Tutorial on Umbrella Sampling Simulation with a Combined QM/MM Potential: The Potential of Mean Force for an SThe journal of physical chemistry. B · 2024Article
- CHARMM at 45: Enhancements in Accessibility, Functionality, and Speed.The journal of physical chemistry. B · 2024Review
- High throughput mutational scanning of a protein via alchemistry on a high-performance computing resource.bioRxiv : the preprint server for biology · 2024Article
- Solution Ionic Strength Can Modulate Functional Loop Conformations inThe journal of physical chemistry. B · 2024Article
- The Catalysis Mechanism ofInternational journal of molecular sciences · 2024Article
- Correlation of temperature dependence of hydride kinetic isotope effects with donor-acceptor distances in two solvents of different polarities.Organic & biomolecular chemistry · 2023Article
- Second-Shell Residues Contribute to Catalysis by Predominately Preorganizing the Apo State in PafA.Journal of the American Chemical Society · 2023Article
- Estimation of frequency factors for the calculation of kinetic isotope effects from classical and path integral free energy simulations.The Journal of chemical physics · 2023Article
- Deuterium Isotope Effects on Acid-Base Equilibrium of Organic Compounds.Molecules (Basel, Switzerland) · 2021Article
- Mechanism of allosteric activation of SIRT6 revealed by the action of rationally designed activators.Acta pharmaceutica Sinica. B · 2021Article
- Distal Regions Regulate Dihydrofolate Reductase-Ligand Interactions.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Tuning Structure and Dynamics of Blue Copper Azurin Junctions via Single Amino-Acid Mutations.Biomolecules · 2019Article
- Substrate-to-Product Conversion Facilitates Active Site Loop Opening in Yeast Enolase: A Molecular Dynamics Study.ACS catalysis · 2019Article
- Control of Solvent Dynamics around the BThe journal of physical chemistry. B · 2019Article
- β-Glucuronidases of opportunistic bacteria are the major contributors to xenobiotic-induced toxicity in the gut.Scientific reports · 2018Article
- Dual QM and MM Approach for Computing Equilibrium Isotope Fractionation Factor of Organic Species in Solution.Molecules (Basel, Switzerland) · 2018Article
- High-pressure protein crystal structure analysis of Escherichia coli dihydrofolate reductase complexed with folate and NADPActa crystallographica. Section D, Structural biology · 2018Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Combined quantum mechanics/molecular mechanics molecular dynamics simulations reveal that the M20 loop conformational dynamics of dihydrofolate reductase (DHFR) is severely restricted at the transition state of the hydride transfer as a result of the M42W/G121V double mutation. Consequently, the double-mutant enzyme has a reduced entropy of activation, i.e., increased entropic barrier, and altered temperature dependence of kinetic isotope effects in comparison with those of wild-type DHFR. Interestingly, in both wild-type DHFR and the double mutant, the average donor-acceptor distances are essentially the same in the Michaelis complex state (~3.5 Å) and the transition state (2.7 Å). It was found that an additional hydrogen bond is formed to stabilize the M20 loop in the closed conformation in the M42W/G121V double mutant. The computational results reflect a similar aim designed to knock out precisely the dynamic flexibility of the M20 loop in a different double mutant, N23PP/S148A.
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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.