A5058944140- Protein Structure and Dynamics
- Spectroscopy and Quantum Chemical Studies
- Advanced Chemical Physics Studies
- RNA Research and Splicing
- Viral Infectious Diseases and Gene Expression in Insects
- Protein purification and stability
- Genetic Neurodegenerative Diseases
- Surfactants and Colloidal Systems
- Monoclonal and Polyclonal Antibodies Research
- Nanopore and Nanochannel Transport Studies
- Graphene research and applications
- Cardiac electrophysiology and arrhythmias
- Advanced Polymer Synthesis and Characterization
- Photoreceptor and optogenetics research
- Photosynthetic Processes and Mechanisms
- Material Dynamics and Properties
- Electrostatics and Colloid Interactions
- Advanced Physical and Chemical Molecular Interactions
- Carbon Nanotubes in Composites
- DNA and Nucleic Acid Chemistry
- Ionic liquids properties and applications
- Mechanical and Optical Resonators
- Polymer Surface Interaction Studies
- Cell Adhesion Molecules Research
- Muscle Physiology and Disorders
CHDI Foundation
2023
GlaxoSmithKline (United States)
2018
Stanford University
2014-2017
Pfizer (United States)
2017
SLAC National Accelerator Laboratory
2014-2016
Menlo School
2016
University of Southern California
2010-2013
National Taiwan University of Science and Technology
2010
St Petersburg University
2007
Recent years have seen tremendous effort in the development of approaches with which to obtain quantum mechanics/molecular mechanics (QM/MM) free energies for reactions condensed phase. Nevertheless, there remain significant challenges address, particularly, high computational cost involved performing proper configurational sampling and, particular, obtaining ab initio QM/MM (QM(ai)/MM) free-energy surfaces. One increasingly popular approach that seems offer an ideal way progress this...
Significance The origin of the activation GTPases is explored considering evidence that transition state for reference solution reaction involves a proton transfer between two water molecules. Ab initio quantum mechanical/molecular mechanical–based calibration empirical valence bond surfaces used to simulate GTPase process. found reflect same type electrostatic stabilization obtained previously single mechanism. step does not appear be rate limiting and thus irrelevant catalytic effect....
The performance of the paradynamics (PD) reference potential approach in QM/MM calculations is examined. It also clarified that, contrast to some possible misunderstandings, this provides a rigorous strategy for free energy calculations. In particular, PD gradual and controlled way improving evaluation perturbation associated with moving from EVB target surface. This achieved by linear response approximation full evaluating changes. We present systematic using Gaussian-based correction...
The nature and mechanism of phosphate hydrolysis reactions are great interest in view the crucial role these key biological processes. Although it is becoming clearer that ultimate way resolving mechanistic controversies must involve reliable theoretical studies, not widely realized such studies cannot be performed at present by using most existing automated ways only careful systematic can lead to meaningful conclusions. work clarifies above point considering monoesters. clarification...
Understanding the nature of free-energy surfaces for phosphate hydrolysis is a prerequisite understanding corresponding key chemical reactions in biology. Here, challenge has been to move careful ab initio QM/MM (QM(ai)/MM) calculations, where obtaining converging results very demanding and computationally expensive. This work describes such focusing on surface monoesters, paying special attention comparison between one water (1W) two (2W) paths proton-transfer (PT) step. issue explored...
RIP2 kinase was recently identified as a therapeutic target for variety of autoimmune diseases. We have reported previously selective 4-aminoquinoline-based inhibitor GSK583 and demonstrated its effectiveness in blocking downstream NOD2 signaling cellular models, rodent vivo human ex disease models. While this tool compound valuable validating the biological pathway, it suffered from activity at hERG ion channel poor PK/PD profile thereby limiting progression analog. Herein, we detail our...
Advances in the synthesis of two-dimensional graphene-like materials (transgraphenes) stimulate interest scientists searching for new elements periodic table that have allotropic modifications. This has led recent years to successful production single-element 2D materials, such as beryllene (Be), indiene (In), molybdenene (Mo) and goldene (Au). In addition, methods creating various derivatives transgraphenes - their compounds with other are actively developing. Moreover, more works recently...
Early identification of asparagine deamidation and aspartate isomerization degradation sites can facilitate the successful development biopharmaceuticals. Several knowledge-based models have been proposed to assess these risks. In this study, we propose a physics-based approach identify on basis free-energy barriers along prechemical conformational step chemical reaction pathway. These contributions are estimated from classical quantum mechanics/molecular mechanics molecular dynamics...
Huntington's disease (HD) is caused by an expanded CAG trinucleotide repeat in exon 1 of the huntingtin (HTT) gene. We report design a series HTT pre-mRNA splicing modulators that lower protein, including toxic mutant (mHTT), promoting insertion pseudoexon containing premature termination codon at 49-50 junction. The resulting transcript undergoes nonsense-mediated decay, leading to reduction mRNA transcripts and protein levels. starting benzamide core was modified pyrazine amide further...
The observed pressure sensitivity of the isomerization reaction rate bis-anthracene cyclophane photoisomer has attracted significant attention in rational design mechanically sensitive materials. However, molecular origin this remains unclear. We developed an ab initio model to quantify effect on and elucidate its origin. Pressure-induced deformations changes along free-energy surfaces are estimated from dynamics trajectories. Our predicts a barrier reduction ∼2 kcal/mol at 0.9 GPa (in...
Proposed in this contribution is a protocol for calculating fine-physics (e.g., ab initio QM/MM) free-energy surfaces at high level of accuracy locally only reactants and the transition state computing activation barrier) from targeted sampling extensive exploratory coarse-physics sampling. The full surface still computed but lower method analytically derived terms umbrella perturbation methods which are combined with thermodynamic cycle strategy paradynamics approach. algorithm starts by...
For a solution of the diblock copolymer composed hydrophobic block and weak polyelectrolyte block, we obtain regions stable aggregate morphologies in pH-solution salinity plane with aid self-consistent field theory strong-segregation approximation. Lamellar, cylindrical, branched spherical aggregates have been considered large interval pH salinity. The morphology stability maps are obtained to help control self-assembly by variation medium. In qualitative agreement experiment, our...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTPressure-Induced Neutral-to-Ionic Transition in an Amorphous Organic MaterialYi Ren†, Semin Lee‡, James M. Christensen†, Nikolay V. Plotnikov§, Mark Burgess†, Todd J. Martínez§, Dana D. Dlott†, and Jeffrey S. Moore*†‡View Author Information† Department of Chemistry, University Illinois at Urbana−Champaign, Urbana, 61801, United States‡ Beckman Institute for Advanced Science Technology, States§ Stanford University, Stanford, California 94305,...
Abstract Human and mouse genetic studies have demonstrated a role for DNA mismatch repair (MMR) molecular machines in modulating the rate of somatic expansion huntingtin ( HTT) CAG repeats, onset progression Huntington’s Disease (HD). MutSβ, key component MMR pathway, is heterodimeric protein MSH2 MSH3 that recognizes initiates extrahelical extrusions. Loss-of-function Msh3 reduced-expression alleles human lead to slower rates delayed disease humans, signifying as promising therapeutic...