The Experts below are selected from a list of 192657 Experts worldwide ranked by ideXlab platform
Anthony C Hunt - One of the best experts on this subject based on the ideXlab platform.
-
dynamics of In Silico leukocyte rollIng activation and adhesion
BMC Systems Biology, 2007Co-Authors: Jonathan Tang, Anthony C HuntAbstract:Background We present a multilevel, agent based, In Silico model that represents the dynamics of rollIng, activation, and adhesion of Individual leukocytes In vitro. Object-oriented software components were designed, verified, plugged together, and then operated In ways that represent the molecular and cellular mechanisms believed responsible for leukocyte rollIng and adhesion. The result is an In Silico analogue of an experimental In vitro system. The experimentally measured, phenotypic attributes of the analogue were compared and contrasted to those of leukocytes In vitro from three different experimental conditions.
-
dynamics of In Silico leukocyte rollIng activation and adhesion
BMC Systems Biology, 2007Co-Authors: Jonathan Tang, Anthony C HuntAbstract:We present a multilevel, agent based, In Silico model that represents the dynamics of rollIng, activation, and adhesion of Individual leukocytes In vitro. Object-oriented software components were designed, verified, plugged together, and then operated In ways that represent the molecular and cellular mechanisms believed responsible for leukocyte rollIng and adhesion. The result is an In Silico analogue of an experimental In vitro system. The experimentally measured, phenotypic attributes of the analogue were compared and contrasted to those of leukocytes In vitro from three different experimental conditions. The Individual In Silico dynamics of "rollIng" on simulated P-selectIn, and separately on simulated VCAM-1, were an acceptable match to Individual In vitro distance-time and velocity-time measurements. The analogues are also able to represent the transition from rollIng to adhesion on P-selectIn and VCAM-1 In the presence of GRO-α chemokIne. The Individual In Silico and In vitro behavioral similarities translated successfully to population level measures. These behavioral similarities were enabled In part by subdividIng the functionality of the analogue's surface Into 600 Independent, "cell"-controlled, equally capable modules of comparable functionality. The overlap In phenotypic attributes of our analogue with those of leukocytes In vitro confirm the considerable potential of our model for studyIng the key events that determIne the behavioral outcome of Individual leukocytes durIng rollIng, activation, and adhesion. Our results provide an important foundation and framework for future In Silico research Into plausible causal lInks between well-documented, subcellular molecular level events and the variety of systemic phenotypic attributes that distInguish normal leukocyte adhesion from abnormal disease-associated adhesion.
Eugene I Shakhnovich - One of the best experts on this subject based on the ideXlab platform.
-
searchIng the sequence space for potent aptamers usIng selex In Silico
Journal of Chemical Theory and Computation, 2015Co-Authors: Qingtong Zhou, Xiaole Xia, Zhaofeng Luo, Haojun Liang, Eugene I ShakhnovichAbstract:To isolate functional nucleic acids that bInd to defIned targets with high affInity and specificity, which are known as aptamers, the systematic evolution of ligands by exponential enrichment (SELEX) methodology has emerged as the preferred approach. Here, we propose a computational approach, SELEX In Silico, that allows the sequence space to be more thoroughly explored regardIng bIndIng of a certaIn target. Our approach consists of two steps: (i) secondary structure-based sequence screenIng, which aims to collect the sequences that can form a desired RNA motif as an enhanced Initial library, followed by (ii) sequence enrichment regardIng target bIndIng by molecular dynamics simulation-based virtual screenIng. Our SELEX In Silico method provided a practical computational solution to three key problems In aptamer sequence searchIng: design of nucleic acid libraries, knowledge of sequence enrichment, and identification of potent aptamers. Six potent theophyllIne-bIndIng aptamers, which were isolated by SELE...
-
searchIng the sequence space for potent aptamers usIng selex In Silico
Journal of Chemical Theory and Computation, 2015Co-Authors: Qingtong Zhou, Xiaole Xia, Zhaofeng Luo, Haojun Liang, Eugene I ShakhnovichAbstract:To isolate functional nucleic acids that bInd to defIned targets with high affInity and specificity, which are known as aptamers, the systematic evolution of ligands by exponential enrichment (SELEX) methodology has emerged as the preferred approach. Here, we propose a computational approach, SELEX In Silico, that allows the sequence space to be more thoroughly explored regardIng bIndIng of a certaIn target. Our approach consists of two steps: (i) secondary structure-based sequence screenIng, which aims to collect the sequences that can form a desired RNA motif as an enhanced Initial library, followed by (ii) sequence enrichment regardIng target bIndIng by molecular dynamics simulation-based virtual screenIng. Our SELEX In Silico method provided a practical computational solution to three key problems In aptamer sequence searchIng: design of nucleic acid libraries, knowledge of sequence enrichment, and identification of potent aptamers. Six potent theophyllIne-bIndIng aptamers, which were isolated by SELEX In Silico from a sequence space contaInIng 4(13) sequences, were experimentally verified to bInd theophyllIne with high affInity: Kd rangIng from 0.16 to 0.52 μM, compared with the dissociation constant of the origInal aptamer-theophyllIne, 0.32 μM. These results demonstrate the significant potential of SELEX In Silico as a new method for aptamer discovery and optimization.
Blanca Rodriguez - One of the best experts on this subject based on the ideXlab platform.
-
In vivo and In Silico Investigation Into mechanisms of frequency dependence of repolarization alternans In human ventricular cardiomyocytes
Circulation Research, 2016Co-Authors: Xin Zhou, Alfonso Buenoorovio, Michele Orini, Ben Hanson, Martin Hayward, Peter Taggart, Pier D Lambiase, Kevin Burrage, Blanca RodriguezAbstract:Rationale: Repolarization alternans (RA) are associated with arrhythmogenesis. Animal studies have revealed potential mechanisms, but human-focused studies are needed. RA generation and frequency dependence may be determIned by cell-to-cell variability In proteIn expression, which is regulated by genetic and external factors. Objective: To characterize In vivo RA In human, and to Investigate In Silico usIng human models the ionic mechanisms underlyIng the frequency-dependent differences In RA behaviour identified In vivo. Methods and Results: In vivo electrograms were acquired at 240 sites coverIng the epicardium of 41 patients at 6 cycle lengths (600-350ms). In Silico Investigations were conducted usIng a population of biophysically-detailed human models IncorporatIng variability In proteIn expression and calibrated usIng In vivo recordIngs. Both In Silico and In vivo, two types of RA were identified, with Fork and Eye-type restitution curves, based on RA persistence or disappearance, respectively, at fast pacIng rates. In Silico simulations show RA are strongly correlated with fluctuations In sarcoplasmic reticulum (SR) calcium, due to strong release and weak reuptake. Large L-type calcium current (I CaL ) conductance is responsible for RA disappearance at fast frequencies In Eye-type (30% larger In Eye-type vs Fork-type, p NaCa is the maIn driver In translatIng Ca 2+ fluctuations Into RA. Conclusions: In human In vivo and In Silico, two types of RA are identified, with RA persistence/disappearance as frequency Increases. In Silico, I CaL and I NaCa determIne RA human cell-to-cell differences through Intracellular and SR Calcium regulation.
-
In vivo and In Silico Investigation Into mechanisms of frequency dependence of repolarization alternans In human ventricular cardiomyocytes
Circulation Research, 2016Co-Authors: Xin Zhou, Alfonso Buenoorovio, Michele Orini, Ben Hanson, Martin Hayward, Peter Taggart, Pier D Lambiase, Kevin Burrage, Blanca RodriguezAbstract:RATIONALE: Repolarization alternans (RA) are associated with arrhythmogenesis. Animal studies have revealed potential mechanisms, but human-focused studies are needed. RA generation and frequency dependence may be determIned by cell-to-cell variability In proteIn expression, which is regulated by genetic and external factors. OBJECTIVE: To characterize In vivo RA In human and to Investigate In Silico usIng human models, the ionic mechanisms underlyIng the frequency-dependent differences In RA behavior identified In vivo. METHODS AND RESULTS: In vivo electrograms were acquired at 240 sites coverIng the epicardium of 41 patients at 6 cycle lengths (600-350 ms). In Silico Investigations were conducted usIng a population of biophysically detailed human models IncorporatIng variability In proteIn expression and calibrated usIng In vivo recordIngs. Both In Silico and In vivo, 2 types of RA were identified, with Fork- and Eye-type restitution curves, based on RA persistence or disappearance, respectively, at fast pacIng rates. In Silico simulations show that RA are strongly correlated with fluctuations In sarcoplasmic reticulum calcium, because of strong release and weak reuptake. Large L-type calcium current conductance is responsible for RA disappearance at fast frequencies In Eye-type (30% larger In Eye-type versus Fork-type; P<0.01), because of sarcoplasmic reticulum Ca(2+) ATPase pump potentiation caused by frequency-Induced Increase In Intracellular calcium. Large Na(+)/Ca(2+) exchanger current is the maIn driver In translatIng Ca(2+) fluctuations Into RA. CONCLUSIONS: In human In vivo and In Silico, 2 types of RA are identified, with RA persistence/disappearance as frequency Increases. In Silico, L-type calcium current and Na(+)/Ca(2+) exchanger current determIne RA human cell-to-cell differences through Intracellular and sarcoplasmic reticulum calcium regulation.
Xiaole Xia - One of the best experts on this subject based on the ideXlab platform.
-
searchIng the sequence space for potent aptamers usIng selex In Silico
Journal of Chemical Theory and Computation, 2015Co-Authors: Qingtong Zhou, Xiaole Xia, Zhaofeng Luo, Haojun Liang, Eugene I ShakhnovichAbstract:To isolate functional nucleic acids that bInd to defIned targets with high affInity and specificity, which are known as aptamers, the systematic evolution of ligands by exponential enrichment (SELEX) methodology has emerged as the preferred approach. Here, we propose a computational approach, SELEX In Silico, that allows the sequence space to be more thoroughly explored regardIng bIndIng of a certaIn target. Our approach consists of two steps: (i) secondary structure-based sequence screenIng, which aims to collect the sequences that can form a desired RNA motif as an enhanced Initial library, followed by (ii) sequence enrichment regardIng target bIndIng by molecular dynamics simulation-based virtual screenIng. Our SELEX In Silico method provided a practical computational solution to three key problems In aptamer sequence searchIng: design of nucleic acid libraries, knowledge of sequence enrichment, and identification of potent aptamers. Six potent theophyllIne-bIndIng aptamers, which were isolated by SELE...
-
searchIng the sequence space for potent aptamers usIng selex In Silico
Journal of Chemical Theory and Computation, 2015Co-Authors: Qingtong Zhou, Xiaole Xia, Zhaofeng Luo, Haojun Liang, Eugene I ShakhnovichAbstract:To isolate functional nucleic acids that bInd to defIned targets with high affInity and specificity, which are known as aptamers, the systematic evolution of ligands by exponential enrichment (SELEX) methodology has emerged as the preferred approach. Here, we propose a computational approach, SELEX In Silico, that allows the sequence space to be more thoroughly explored regardIng bIndIng of a certaIn target. Our approach consists of two steps: (i) secondary structure-based sequence screenIng, which aims to collect the sequences that can form a desired RNA motif as an enhanced Initial library, followed by (ii) sequence enrichment regardIng target bIndIng by molecular dynamics simulation-based virtual screenIng. Our SELEX In Silico method provided a practical computational solution to three key problems In aptamer sequence searchIng: design of nucleic acid libraries, knowledge of sequence enrichment, and identification of potent aptamers. Six potent theophyllIne-bIndIng aptamers, which were isolated by SELEX In Silico from a sequence space contaInIng 4(13) sequences, were experimentally verified to bInd theophyllIne with high affInity: Kd rangIng from 0.16 to 0.52 μM, compared with the dissociation constant of the origInal aptamer-theophyllIne, 0.32 μM. These results demonstrate the significant potential of SELEX In Silico as a new method for aptamer discovery and optimization.
Qingtong Zhou - One of the best experts on this subject based on the ideXlab platform.
-
searchIng the sequence space for potent aptamers usIng selex In Silico
Journal of Chemical Theory and Computation, 2015Co-Authors: Qingtong Zhou, Xiaole Xia, Zhaofeng Luo, Haojun Liang, Eugene I ShakhnovichAbstract:To isolate functional nucleic acids that bInd to defIned targets with high affInity and specificity, which are known as aptamers, the systematic evolution of ligands by exponential enrichment (SELEX) methodology has emerged as the preferred approach. Here, we propose a computational approach, SELEX In Silico, that allows the sequence space to be more thoroughly explored regardIng bIndIng of a certaIn target. Our approach consists of two steps: (i) secondary structure-based sequence screenIng, which aims to collect the sequences that can form a desired RNA motif as an enhanced Initial library, followed by (ii) sequence enrichment regardIng target bIndIng by molecular dynamics simulation-based virtual screenIng. Our SELEX In Silico method provided a practical computational solution to three key problems In aptamer sequence searchIng: design of nucleic acid libraries, knowledge of sequence enrichment, and identification of potent aptamers. Six potent theophyllIne-bIndIng aptamers, which were isolated by SELE...
-
searchIng the sequence space for potent aptamers usIng selex In Silico
Journal of Chemical Theory and Computation, 2015Co-Authors: Qingtong Zhou, Xiaole Xia, Zhaofeng Luo, Haojun Liang, Eugene I ShakhnovichAbstract:To isolate functional nucleic acids that bInd to defIned targets with high affInity and specificity, which are known as aptamers, the systematic evolution of ligands by exponential enrichment (SELEX) methodology has emerged as the preferred approach. Here, we propose a computational approach, SELEX In Silico, that allows the sequence space to be more thoroughly explored regardIng bIndIng of a certaIn target. Our approach consists of two steps: (i) secondary structure-based sequence screenIng, which aims to collect the sequences that can form a desired RNA motif as an enhanced Initial library, followed by (ii) sequence enrichment regardIng target bIndIng by molecular dynamics simulation-based virtual screenIng. Our SELEX In Silico method provided a practical computational solution to three key problems In aptamer sequence searchIng: design of nucleic acid libraries, knowledge of sequence enrichment, and identification of potent aptamers. Six potent theophyllIne-bIndIng aptamers, which were isolated by SELEX In Silico from a sequence space contaInIng 4(13) sequences, were experimentally verified to bInd theophyllIne with high affInity: Kd rangIng from 0.16 to 0.52 μM, compared with the dissociation constant of the origInal aptamer-theophyllIne, 0.32 μM. These results demonstrate the significant potential of SELEX In Silico as a new method for aptamer discovery and optimization.
