scholarly journals Analytical and Computational Methods for the Assessment of Biological Molecules and their Binding Interactions: Case Studies in DNA Aptamer-Target Binding and P450-P450 Dimerization

2015 ◽  
Author(s):  
Katherine M. Hickey
Keyword(s):  
Case Studies ◽  
Computational Methods ◽  
Biological Molecules ◽  
Dna Aptamer ◽  
Binding Interactions ◽  
Target Binding

scholarly journals Emergent synthetic methods for the modular advancement of sp3-rich fragments

2021 ◽  
Vol 12 (13) ◽  
pp. 4646-4660
Author(s):  
Max J. Caplin ◽  
Daniel J. Foley
Keyword(s):  
Synthetic Methods ◽  
Binding Interactions ◽  
Target Binding

This Perspective reviews recently developed methods that are likely to be of value to the elaboration of sp3-rich fragments from carbon-centred vectors, whilst maintaining key fragment-to-target binding interactions.

Construction of Agri-Environmental Data Using Computational Methods

2011 ◽  
pp. 727-748
Author(s):  
Susumu Uchida ◽  
Kiyotada Hayashi ◽  
Masaei Sato ◽  
Shingo Hokazono
Keyword(s):  
Developing Countries ◽  
Life Cycle ◽  
Case Studies ◽  
Computational Methods ◽  
Production Systems ◽  
Environmental Data ◽  
Agricultural Sustainability ◽  
Special Focus ◽  
Japanese Case ◽  
Database Construction

Increased public focus on agri-environmental issues and recent policies on agricultural sustainability have necessitated the construction of a life cycle inventory (LCI) database for agricultural production systems. However, the current progress of LCI database construction is far from being complete in both developed and developing countries. In this chapter, an integrated view for a data-construction methodology for agri-environmental assessment is proposed. The applications of computational methods to the construction processes are also proposed, with a special focus on Japanese case studies. After discussing the methods for construction, the implications of LCI construction are presented, which includes the following issues: how to make a transition to sustainability, and how to achieve informed and science-based policy decisions by increasing the applicability of life cycle assessment and the level of preparedness. The Japanese case studies should support assessment and decisions in developed and developing countries.

scholarly journals An engineered one-site aptamer with higher sensitivity for label-free detection of adenosine on graphene oxide

2018 ◽  
Vol 96 (11) ◽  
pp. 957-963 ◽  
Author(s):  
Zijie Zhang ◽  
Juewen Liu
Keyword(s):  
Graphene Oxide ◽  
Binding Sites ◽  
Dna Aptamer ◽  
Stem Length ◽  
Titration Calorimetry ◽  
Label Free ◽  
Label Free Detection ◽  
Analytical Perspective ◽  
Target Binding ◽  
The One

The 27-nucleotide DNA aptamer for adenosine and ATP, originally selected by the Szostak lab in 1995, has been a very popular model system for biosensor development. This unique aptamer has two target binding sites, and we recently showed that it is possible to remove either site while the other one still retains binding. From an analytical perspective, tuning the number of binding sites has important implications in modulating sensitivity of the resulting biosensors. In this work, we report that the engineered one-site aptamer showed excellent signaling properties with a 2.6-fold stronger signal intensity and also a 4.2-fold increased detection limit compared with the wild-type two-site aptamer. The aptamer has a hairpin structure, and the length of the hairpin stem was systematically varied for the one-site aptamers. Isothermal titration calorimetry and a label-free fluorescence signaling method with graphene oxide and SYBR Green I were respectively used to evaluate binding and sensor performance. Although longer stemmed aptamers produced better adenosine binding affinity, the signaling was quite independent of the stem length as long as more than three base pairs were left. This was explained by the higher affinity of binding to GO by the longer aptamers, cancelling out the higher affinity for adenosine binding. This work further confirms the analytical applications of such one-site adenosine aptamers, which are potentially useful for improved ATP imaging and for developing new biosensors.

Diastereoselective N-quaternization of piperidines

2015 ◽  
Vol 93 (4) ◽  
pp. 468-476 ◽  
Author(s):  
Christine R. Dunbar ◽  
F.G. West
Keyword(s):  
Ionic Liquids ◽  
Case Studies ◽  
Computational Methods ◽  
Phase Transfer ◽  
Experimental Results ◽  
Ammonium Salts ◽  
Chiral Catalysts ◽  
Simple Reaction

The study of the N-quaternization of substituted piperidines has been mostly dormant for the last 40 years, despite the demand for ammonium salts as drugs, ionic liquids, chiral catalysts or ligands, phase transfer reagents, and reagents for the Stevens and Sommelet–Hauser rearrangements. In this perspective article, the complexity of this seemingly simple reaction is studied by a summary and analysis of literature experimental results. Computational methods are applied to various literature reactions as case studies.

scholarly journals GIC: A computational method for predicting the essentiality of long noncoding lncRNAs

2017 ◽  
Author(s):  
Pan Zeng ◽  
Ji Chen ◽  
Yuan Zhou ◽  
Jichun Yang ◽  
Qinghua Cui
Keyword(s):  
Computational Methods ◽  
High Performance ◽  
Noncoding Rnas ◽  
Web Server ◽  
Long Noncoding Rnas ◽  
Computational Method ◽  
Biological Molecules ◽  
Sequence Information ◽  
Protein Coding ◽  
Protein Coding Genes

ABSTRACTMeasuring the essentiality of genes is critically important in biology and medicine. Some bioinformatic methods have been developed for this issue but none of them can be applied to long noncoding RNAs (lncRNAs), one big class of biological molecules. Here we developed a computational method, GIC (Gene Importance Calculator), which can predict the essentiality of both protein-coding genes and lncRNAs based on RNA sequence information. For identifying the essentiality of protein-coding genes, GIC is competitive with well-established computational scores. More important, GIC showed a high performance for predicting the essentiality of lncRNAs. In an independent mouse lncRNA dataset, GIC achieved an exciting performance (AUC=0.918). In contrast, the traditional computational methods are not applicable to lncRNAs. As a public web server, GIC is freely available at http://www.cuilab.cn/gic/.

scholarly journals Computer-guided Binding Mode Identification and Affinity Improvement of an LRR Protein Binder without Structure Determination

2019 ◽  
Author(s):  
Yoonjoo Choi ◽  
Sukyo Jeong ◽  
Jung-Min Choi ◽  
Christian Ndong ◽  
Chris Bailey-Kellogg ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Binding Affinity ◽  
Computational Methods ◽  
Structure Determination ◽  
Binding Mode ◽  
Leucine Rich Repeat ◽  
Human Igg ◽  
Mode Identification ◽  
Target Binding ◽  
Lrr Protein

AbstractPrecise binding mode identification and subsequent affinity improvement without structure determination remain a challenge in the development of therapeutic proteins. However, relevant experimental techniques are generally quite costly, and purely computational methods have been unreliable. Here, we show that integrated computational and experimental epitope localization followed by full-atom energy minimization can yield an accurate complex model structure which ultimately enables effective affinity improvement and redesign of binding specificity. As proof-of-concept, we used a leucine-rich repeat (LRR) protein binder, called a repebody (Rb), that specifically recognizes human IgG1 (hIgG1). We performed computationally-guided identification of the Rb:hIgG1 binding mode and leveraged the resulting model to reengineer the Rb so as to significantly increase its binding affinity for hIgG1 as well as redesign its specificity toward multiple IgGs from other species. Experimental structure determination verified that our Rb:hIgG1 model closely matched the co-crystal structure. Using a benchmark of other LRR protein complexes, we further demonstrated that the present approach may be broadly applicable to proteins undergoing relatively small conformational changes upon target binding.Author SummaryIt is quite challenging for computational methods to determine how proteins interact and to design mutations to alter their binding affinity and specificity. Despite recent advances in computational methods, however, in silico evaluation of binding energies has proven to be extremely difficult. We show that, in the case of protein-protein interactions where only small structural changes occur upon target binding, an integrated computational and experimental approach can identify a binding mode and drive reengineering efforts to improve binding affinity or specificity. Using as a model system a leucine-rich repeat (LRR) protein binder that recognizes human IgG1, our approach yielded a model of the protein complex that was very similar to the subsequently experimentally determined co-crystal structure, and enabled design of variants with significantly improved IgG1 binding affinity and with the ability to recognize IgG1 from other species.

scholarly journals Impact of the Position of the Chemically Modified 5-Furyl-2′-Deoxyuridine Nucleoside on the Thrombin DNA Aptamer–Protein Complex: Structural Insights into Aptamer Response from MD Simulations

Molecules ◽  
2019 ◽  
Vol 24 (16) ◽  
pp. 2908 ◽  
Author(s):  
Preethi Seelam Prabhakar ◽  
Richard A. Manderville ◽  
Stacey D. Wetmore
Keyword(s):  
Binding Affinity ◽  
Structural Changes ◽  
Experimental Studies ◽  
Local Environment ◽  
Md Simulations ◽  
Fine Tuning ◽  
Dna Aptamer ◽  
Solvent Exposure ◽  
Chemically Modified ◽  
Target Binding

Aptamers are functional nucleic acids that bind to a range of targets (small molecules, proteins or cells) with a high affinity and specificity. Chemically-modified aptamers are of interest because the incorporation of novel nucleobase components can enhance aptamer binding to target proteins, while fluorescent base analogues permit the design of functional aptasensors that signal target binding. However, since optimally modified nucleoside designs have yet to be identified, information about how to fine tune aptamer stability and target binding affinity is required. The present work uses molecular dynamics (MD) simulations to investigate modifications to the prototypical thrombin-binding aptamer (TBA), which is a 15-mer DNA sequence that folds into a G-quadruplex structure connected by two TT loops and one TGT loop. Specifically, we modeled a previously synthesized thymine (T) analog, namely 5-furyl-2′-deoxyuridine (5FurU), into each of the six aptamer locations occupied by a thymine base in the TT or TGT loops of unbound and thrombin bound TBA. This modification and aptamer combination were chosen as a proof-of-principle because previous experimental studies have shown that TBA displays emissive sensitivity to target binding based on the local environment polarity at different 5FurU modification sites. Our simulations reveal that the chemically-modified base imparts noticeable structural changes to the aptamer without affecting the global conformation. Depending on the modification site, 5FurU performance is altered due to changes in the local environment, including the modification site structural dynamics, degree of solvent exposure, stacking with neighboring bases, and interactions with thrombin. Most importantly, these changes directly correlate with the experimentally-observed differences in the stability, binding affinity and emissive response of the modified aptamers. Therefore, the computational protocols implemented in the present work can be used in subsequent studies in a predictive way to aid the fine tuning of aptamer target recognition for use as biosensors (aptasensors) and/or therapeutics.

Manipulation of a DNA aptamer–protein binding site through arylation of internal guanine residues

2018 ◽  
Vol 16 (20) ◽  
pp. 3831-3840 ◽  
Author(s):  
Abigail J. Van Riesen ◽  
Kaila L. Fadock ◽  
Prashant S. Deore ◽  
Ahmed Desoky ◽  
Richard A. Manderville ◽  
...  
Keyword(s):  
Protein Binding ◽  
Binding Site ◽  
Binding Affinity ◽  
Target Recognition ◽  
Molecular Target ◽  
Dna Aptamer ◽  
Protein Binding Site ◽  
Chemically Modified ◽  
Structure Activity ◽  
Target Binding

Chemically modified aptamers have the opportunity to increase aptamer target binding affinity and provide structure–activity relationships to enhance our understanding of molecular target recognition by the aptamer fold.

scholarly journals Sequence and Structure Analysis of Biological Molecules Based on Computational Methods

2015 ◽  
Vol 2015 ◽  
pp. 1-3
Author(s):  
Jia-Feng Yu ◽  
Yue-Dong Yang ◽  
Xiao Sun ◽  
Ji-Hua Wang
Keyword(s):  
Structure Analysis ◽  
Computational Methods ◽  
Biological Molecules
Sign in / Sign up

Export Citation Format

Share Document