Towards Accurate Ab Initio QM/MM Calculations of Free-Energy Profiles of Enzymatic Reactions

2006 ◽  
Vol 110 (6) ◽  
pp. 2934-2941 ◽  
Author(s):  
Edina Rosta ◽  
Marco Klähn ◽  
Arieh Warshel
Keyword(s):  
Free Energy ◽  
Ab Initio ◽  
Enzymatic Reactions ◽  
Energy Profiles ◽  
Free Energy Profiles

scholarly journals Accelerated Computation of Free Energy Profile at ab Initio Quantum Mechanical/Molecular Mechanics Accuracy via a Semi-Empirical Reference Potential. II. Recalibrating Semi-Empirical Parameters with Force Matching

2019 ◽  
Author(s):  
Xiaoliang Pan ◽  
Pengfei Li ◽  
Junming Ho ◽  
Jingzhi Pu ◽  
Ye Mei ◽  
...  
Keyword(s):  
Free Energy ◽  
Ab Initio ◽  
Quantum Mechanical ◽  
Energy Profile ◽  
Free Energy Profile ◽  
Force Matching ◽  
Energy Profiles ◽  
Reference Potential ◽  
Semi Empirical ◽  
Free Energy Profiles

An efficient and accurate reference potential simulation protocol is proposed for producing ab initio quantum mechanical molecular mechanical (AI-QM/MM) quality free energy profiles for chemical<br>reactions in a solvent or macromolecular environment. This protocol involves three stages: (a) using force matching to recalibrate a semi-empirical quantum mechanical (SE-QM) Hamiltonian for the specific reaction under study; (b) employing the recalibrated SE-QM Hamiltonian (in combination with molecular mechanical force fields) as the reference potential to drive umbrella samplings along the reaction pathway; and (c) computing AI-QM/MM energy values for collected configurations from the sampling and performing weighted thermodynamic perturbation to acquire AI-QM/MM corrected reaction free energy profile. For three model reactions (identity SN2 reaction, Menshutkin reaction, and glycine proton transfer reaction) in aqueous solution and one enzyme reaction (Claisen arrangement in chorismate mutase), our simulations using recalibrated PM3 SE-QM Hamiltonians well reproduced AI-QM/MM free energy profiles (at the B3LYP/6-31G* level of theory) all within 1 kcal/mol with a 20 to 45 fold reduction in the computer time.

scholarly journals Accelerated computation of free energy profile at ab initio quantum mechanical/molecular mechanical accuracy via a semi-empirical reference potential. II. Recalibrating semi-empirical parameters with force matching

2019 ◽  
Vol 21 (37) ◽  
pp. 20595-20605 ◽  
Author(s):  
Xiaoliang Pan ◽  
Pengfei Li ◽  
Junming Ho ◽  
Jingzhi Pu ◽  
Ye Mei ◽  
...  
Keyword(s):  
Free Energy ◽  
Ab Initio ◽  
Quantum Mechanical ◽  
Energy Profile ◽  
Force Matching ◽  
Energy Profiles ◽  
Reference Potential ◽  
Simulation Protocol ◽  
Semi Empirical ◽  
Free Energy Profiles

An efficient and accurate reference potential simulation protocol is proposed for producing ab initio quantum mechanical/molecular mechanical (AI-QM/MM) quality free energy profiles for chemical reactions in a solvent or macromolecular environment.

Ab Initio Modeling of Free Energy Profiles in Thermally Activated Processes

2002 ◽  
pp. 19-29
Author(s):  
I. Štich ◽  
M. Hytha ◽  
J. D. Gale ◽  
K. Terakura ◽  
M. C. Payne
Keyword(s):  
Free Energy ◽  
Ab Initio ◽  
Thermally Activated ◽  
Ab Initio Modeling ◽  
Energy Profiles ◽  
Activated Processes ◽  
Free Energy Profiles

scholarly journals Accelerated Computation of Free Energy Profile at ab Initio Quantum Mechanical/Molecular Mechanics Accuracy via a Semi-Empirical Reference Potential. II. Recalibrating Semi-Empirical Parameters with Force Matching

2019 ◽  
Author(s):  
Xiaoliang Pan ◽  
Pengfei Li ◽  
Junming Ho ◽  
Jingzhi Pu ◽  
Ye Mei ◽  
...  
Keyword(s):  
Free Energy ◽  
Ab Initio ◽  
Quantum Mechanical ◽  
Energy Profile ◽  
Free Energy Profile ◽  
Force Matching ◽  
Energy Profiles ◽  
Reference Potential ◽  
Semi Empirical ◽  
Free Energy Profiles

An efficient and accurate reference potential simulation protocol is proposed for producing ab initio quantum mechanical molecular mechanical (AI-QM/MM) quality free energy profiles for chemical<br>reactions in a solvent or macromolecular environment. This protocol involves three stages: (a) using force matching to recalibrate a semi-empirical quantum mechanical (SE-QM) Hamiltonian for the specific reaction under study; (b) employing the recalibrated SE-QM Hamiltonian (in combination with molecular mechanical force fields) as the reference potential to drive umbrella samplings along the reaction pathway; and (c) computing AI-QM/MM energy values for collected configurations from the sampling and performing weighted thermodynamic perturbation to acquire AI-QM/MM corrected reaction free energy profile. For three model reactions (identity SN2 reaction, Menshutkin reaction, and glycine proton transfer reaction) in aqueous solution and one enzyme reaction (Claisen arrangement in chorismate mutase), our simulations using recalibrated PM3 SE-QM Hamiltonians well reproduced AI-QM/MM free energy profiles (at the B3LYP/6-31G* level of theory) all within 1 kcal/mol with a 20 to 45 fold reduction in the computer time.

scholarly journals Particle Diffusivity and Free-Energy Profiles in Hydrogels from Time-Resolved Penetration Data

2021 ◽  
Author(s):  
Amanuel Wolde-Kidan ◽  
Anna Herrmann ◽  
Albert Prause ◽  
Michael Gradzielski ◽  
Rainer Haag ◽  
...  
Keyword(s):  
Free Energy ◽  
Time Resolved ◽  
Energy Profiles ◽  
Penetration Data ◽  
Free Energy Profiles

Free energy profile analysis to identify factors activating the aggregation-induced emission of a cyanostilbene derivative

2021 ◽  
Author(s):  
Norifumi Yamamoto
Keyword(s):  
Free Energy ◽  
Profile Analysis ◽  
Energy Profile ◽  
Contributing Factors ◽  
Free Energy Profile ◽  
Aggregation Induced Emission ◽  
Energy Profiles ◽  
Free Energy Profiles

The contributing factors that cause the aggregation-induced emission (AIE) are determined by identifying characteristic differences in the free energy profiles of the AIE processes of the AIE-active E-form of CN-MBE and the inactive Z-form.

Chemical free energy profiles for martensitic transformation of CuAlNi at finite temperatures

2021 ◽  
Vol 195 ◽  
pp. 110478
Author(s):  
Zewei Li ◽  
Hengshan Hu ◽  
Yubao Zhen
Keyword(s):  
Free Energy ◽  
Martensitic Transformation ◽  
Energy Profiles ◽  
Chemical Free Energy ◽  
Free Energy Profiles

scholarly journals Reconstructing the Free Energy Profiles Describing the Switching Mechanism of a pH-Dependent DNA Nanodevice from ABMD Simulations

2021 ◽  
Vol 11 (9) ◽  
pp. 4052
Author(s):  
Alice Romeo ◽  
Mattia Falconi ◽  
Alessandro Desideri ◽  
Federico Iacovelli
Keyword(s):  
Free Energy ◽  
Double Helix ◽  
Minimum Energy ◽  
Switching Mechanism ◽  
Linker Length ◽  
Energy Profiles ◽  
Functional Dna ◽  
Triplex Forming Oligonucleotide ◽  
Dynamics Simulations ◽  
Free Energy Profiles

The pH-responsive behavior of six triple-helix DNA nanoswitches, differing in the number of protonation centers (two or four) and in the length of the linker (5, 15 or 25 bases), connecting the double-helical region to the single-strand triplex-forming region, was characterized at the atomistic level through Adaptively Biased Molecular Dynamics simulations. The reconstruction of the free energy profiles of triplex-forming oligonucleotide unbinding from the double helix identified a different minimum energy path for the three diprotic nanoswitches, depending on the length of the connecting linker and leading to a different per-base unbinding profile. The same analyses carried out on the tetraprotic switches indicated that, in the presence of four protonation centers, the unbinding process occurs independently of the linker length. The simulation data provide an atomistic explanation for previously published experimental results showing, only in the diprotic switch, a two unit increase in the pKa switching mechanism decreasing the linker length from 25 to 5 bases, endorsing the validity of computational methods for the design and refinement of functional DNA nanodevices.

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