Simulated scaling method for localized enhanced sampling and simultaneous “alchemical” free energy simulations: A general method for molecular mechanical, quantum mechanical, and quantum mechanical/molecular mechanical simulations

2007 ◽  
Vol 126 (2) ◽  
pp. 024106 ◽  
Author(s):  
Hongzhi Li ◽  
Mikolai Fajer ◽  
Wei Yang
Keyword(s):  
Free Energy ◽  
Quantum Mechanical ◽  
Enhanced Sampling ◽  
Scaling Method ◽  
Energy Simulations ◽  
Alchemical Free Energy ◽  
General Method

Chaperoned alchemical free energy simulations: A general method for QM, MM, and QM/MM potentials

2004 ◽  
Vol 120 (20) ◽  
pp. 9450-9453 ◽  
Author(s):  
Wei Yang ◽  
Ryan Bitetti-Putzer ◽  
Martin Karplus
Keyword(s):  
Free Energy ◽  
Energy Simulations ◽  
Alchemical Free Energy ◽  
General Method

Quantum Mechanical/Molecular Mechanical Free Energy Simulations of the GlutathioneS-Transferase (M1-1) Reaction with Phenanthrene 9,10-Oxide

2002 ◽  
Vol 124 (33) ◽  
pp. 9926-9936 ◽  
Author(s):  
Lars Ridder ◽  
Ivonne M. C. M. Rietjens ◽  
Jacques Vervoort ◽  
Adrian J. Mulholland
Keyword(s):  
Free Energy ◽  
Quantum Mechanical ◽  
Energy Simulations

scholarly journals Role of the Active Site Guanine in theglmSRibozyme Self-Cleavage Mechanism: Quantum Mechanical/Molecular Mechanical Free Energy Simulations

2015 ◽  
Vol 137 (2) ◽  
pp. 784-798 ◽  
Author(s):  
Sixue Zhang ◽  
Abir Ganguly ◽  
Puja Goyal ◽  
Jamie L. Bingaman ◽  
Philip C. Bevilacqua ◽  
...  
Keyword(s):  
Free Energy ◽  
Active Site ◽  
Quantum Mechanical ◽  
Energy Simulations

scholarly journals Substrate Specificity for Human Histidine Methyltransferase SETD3

2021 ◽  
Author(s):  
Jordi Hintzen ◽  
Huida Ma ◽  
Hao Deng ◽  
Apolonia Witecka ◽  
Steffen B. Andersen ◽  
...  
Keyword(s):  
Free Energy ◽  
Energy Barrier ◽  
Human Biology ◽  
Quantum Mechanical ◽  
Enzyme Assays ◽  
Free Energy Barrier ◽  
Methyl Transfer ◽  
Energy Simulations ◽  
Computational Analyses ◽  
Insight Into

Histidine methyltransferase SETD3 plays an important role in human biology and diseases. Previously, we showed that SETD3 catalyzes N3-methylation of histidine 73 in β-actin (Kwiatkowski et al., 2018). Here we report integrated synthetic, biocatalytic, biostructural and computational analyses on human SETD3-catalyzed methylation of β-actin peptides possessing histidine and its structurally and chemically diverse mimics. Our enzyme assays supported by biostructural analyses demonstrate that SETD3 has a broader substrate scope beyond histidine, including N-nucleophiles on the aromatic and aliphatic side chains. Quantum mechanical/molecular mechanical (QM/MM) molecular dynamics and free-energy simulations provide insight into binding geometries and the free energy barrier for the enzymatic methyl transfer to histidine mimics, further supporting experimental data that histidine is the superior SETD3 substrate over its analogs. This work demonstrates that human SETD3 has a potential to catalyze efficient methylation of several histidine mimics, overall providing mechanistic, biocatalytic and functional insight into β-actin histidine methylation by SETD3.

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