QM/MM Free-Energy Simulations of Reaction in Serratia marcescens Chitinase B Reveal the Protonation State of Asp142 and the Critical Role of Tyr214

2014 ◽  
Vol 118 (18) ◽  
pp. 4771-4783 ◽  
Author(s):  
Jitrayut Jitonnom ◽  
Michael A. L. Limb ◽  
Adrian J. Mulholland
Keyword(s):  
Free Energy ◽  
Serratia Marcescens ◽  
Critical Role ◽  
Protonation State ◽  
Energy Simulations

scholarly journals The Free-Energy Landscape of the di-Nucleosome: A Critical Role of the H4 Tails for the Nucleosome-Nucleosome Conformation

2017 ◽  
Vol 112 (3) ◽  
pp. 216a
Author(s):  
Hisashi Ishida ◽  
Hidetoshi Kono
Keyword(s):  
Free Energy ◽  
Energy Landscape ◽  
Critical Role ◽  
Free Energy Landscape

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

The Role of Bonded Terms in Free Energy Simulations. 2. Calculation of Their Influence on Free Energy Differences of Solvation

1999 ◽  
Vol 103 (1) ◽  
pp. 119-136 ◽  
Author(s):  
Stefan Boresch ◽  
Martin Karplus
Keyword(s):  
Free Energy ◽  
Energy Simulations

The Role of Bonded Terms in Free Energy Simulations:  1. Theoretical Analysis

1999 ◽  
Vol 103 (1) ◽  
pp. 103-118 ◽  
Author(s):  
Stefan Boresch ◽  
Martin Karplus
Keyword(s):  
Free Energy ◽  
Theoretical Analysis ◽  
Energy Simulations

The Role of Bonded Energy Terms in Free Energy Simulations - Insights from Analytical Results

2002 ◽  
Vol 28 (1-2) ◽  
pp. 13-37 ◽  
Author(s):  
Stefan Boresch
Keyword(s):  
Free Energy ◽  
Analytical Results ◽  
Energy Simulations

scholarly journals Exploring the Role of the Third Active Site Metal Ion in DNA Polymerase η with QM/MM Free Energy Simulations

2018 ◽  
Vol 140 (28) ◽  
pp. 8965-8969 ◽  
Author(s):  
David R. Stevens ◽  
Sharon Hammes-Schiffer
Keyword(s):  
Free Energy ◽  
Dna Polymerase ◽  
Active Site ◽  
Metal Ion ◽  
The Third ◽  
Energy Simulations

Acid–base equilibrium of the chromophore counterion results in distinct photoisomerization reactivity in the primary event of proteorhodopsin

2019 ◽  
Vol 21 (46) ◽  
pp. 25728-25734
Author(s):  
Chun-Fu Chang ◽  
Hikaru Kuramochi ◽  
Manish Singh ◽  
Rei Abe-Yoshizumi ◽  
Tatsuya Tsukuda ◽  
...  
Keyword(s):  
Schiff Base ◽  
Critical Role ◽  
Ultrafast Dynamics ◽  
Protonation State ◽  
Primary Event ◽  
Acid Base ◽  
Time Resolved ◽  
Base Equilibrium ◽  
Acid Base Equilibrium

Femtosecond time-resolved absorption highlights the critical role of the protonation state of Schiff base counterions in ultrafast dynamics of proteorhodopsin.

scholarly journals Exploring the Free Energy Landscape and Thermodynamics of Protein-Protein Association: HIV-1 Integrase Multimerization Induced by an Allosteric Inhibitor

2020 ◽  
Author(s):  
C. Tse ◽  
L. Wickstrom ◽  
M. Kvaratskhelia ◽  
E. Gallicchio ◽  
R. Levy ◽  
...  
Keyword(s):  
Free Energy ◽  
Energy Landscape ◽  
Critical Role ◽  
Configurational Entropy ◽  
Umbrella Sampling ◽  
Free Energy Landscape ◽  
Drug Induced ◽  
Protein Association ◽  
Hiv 1

AbstractWe report the free energy landscape and thermodynamics of the protein-protein association responsible for the drug-induced multimerization of HIV-1 integrase (IN). Allosteric HIV-1 integrase inhibitors (ALLINIs) promote aberrant IN multimerization by bridging IN-IN intermolecular interactions. However, the thermodynamic driving forces and kinetics of the multimerization remain largely unknown. Here we explore the early steps in the IN multimerization by using umbrella sampling and unbiased molecular dynamics simulations in explicit solvent. In direct simulations, the two initially separated dimers spontaneously associate to form near-native complexes that resemble the crystal structure of the aberrant tetramer. Most strikingly, the effective interaction of the protein-protein association is very short-ranged: the two dimers associate rapidly within tens of nanoseconds when their binding surfaces are separated by d ≤ 4.3 Å (less than two water diameters). Beyond this distance, the oligomerization kinetics appears to be diffusion controlled with a much longer association time. The free energy profile also captured the crucial role of ALLINI in promoting multimerization, and explained why several CTD mutations are remarkably resistant to the drug-induced multimerization. The results also show that at small separation the protein-protein binding process contains two consecutive phases with distinct thermodynamic signatures. First, inter-protein water molecules are expelled to the bulk resulting in a small increase in entropy, as the solvent entropy gain from the water release is nearly cancelled by the loss of side chain entropies as the two proteins approach each other. At shorter distances, the two dry binding surfaces adapt to each other to optimize their interaction energy at the expense of further protein configurational entropy loss. While the binding interfaces feature clusters of hydrophobic residues, overall, the protein-protein association in this system is driven by enthalpy and opposed by entropy.Statement of SignificanceElucidating the energetics and thermodynamic aspects of protein-protein association is important for understanding this fundamental biophysical process. This study provided a more complete physical picture of the protein-protein association responsible for the drug-induced HIV-1 integrase multimerization. The results captured the critical role of the inhibitor, and accounted for the effects of mutations on the protein association. Remarkably, the effective range of the protein-protein attractive funnel is found to be very short, at less than two layers of water, despite the fact that the two binding partners carry opposite net charges. Lastly, entropy/enthalpy decomposition shows that the solvent release from the inter-protein region into the bulk is more than offset by the loss of the solute configurational entropy due to complexation.

The Role of the SLP in Autism Spectrum Disorder Screening and Assessment

2008 ◽  
Vol 15 (2) ◽  
pp. 50-59 ◽  
Author(s):  
Amy Philofsky
Keyword(s):  
Language Development ◽  
Critical Role ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Children With Asd ◽  
Prevalence Estimates ◽  
Notable Increase ◽  
Screening Assessment ◽  
Critical Components

AbstractRecent prevalence estimates for autism have been alarming as a function of the notable increase. Speech-language pathologists play a critical role in screening, assessment and intervention for children with autism. This article reviews signs that may be indicative of autism at different stages of language development, and discusses the importance of several psychometric properties—sensitivity and specificity—in utilizing screening measures for children with autism. Critical components of assessment for children with autism are reviewed. This article concludes with examples of intervention targets for children with ASD at various levels of language development.

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