Topics

NMR-based fragment screening and lead discovery accelerated by principal component analysis.

08:00 EDT 20th September 2019 | BioPortfolio

Summary of "NMR-based fragment screening and lead discovery accelerated by principal component analysis."

Protein-based NMR spectroscopy has proven to be a very robust method for finding fragment leads to protein targets. However, one limitation of protein-based NMR is that the data acquisition and analysis can be time consuming. In order to streamline the scoring of protein-based NMR fragment screening data and the determination of ligand affinities using 2D NMR experiments we have developed a data analysis workflow based on principal component analysis (PCA) within the TREND NMR Pro software package. We illustrate this using four different proteins and sets of ligands which interact with these proteins over a range of affinities. Also, these PCA-based methods can be successfully applied even to systems where ligand binding to target proteins is in intermediate or even slow exchange on the NMR time scale. Finally, these methods will work for scoring of fragment binding data using protein spectra that are either highly overlapped or lower in resolution.

Affiliation

Journal Details

This article was published in the following journal.

Name: Journal of biomolecular NMR
ISSN: 1573-5001
Pages:

Links

DeepDyve research library

PubMed Articles [23703 Associated PubMed Articles listed on BioPortfolio]

Fragments: where are we now?

Fragment-based drug discovery (FBDD) has become a mainstream technology for the identification of chemical hit matter in drug discovery programs. To date, the food and drug administration has approved...

Fragment-based drug discovery using cryo-EMs.

Recent advances in cryo-electron microscopy (EM) structure determination have pushed the resolutions obtainable by the method into the range widely considered to be of utility for drug discovery. Here...

Discovery of a Bromodomain and Extraterminal Inhibitor with a Low Predicted Human Dose through Synergistic Use of Encoded Library Technology and Fragment Screening.

The bromodomain and extraterminal (BET) family of bromodomain-containing proteins are important regulators of the epigenome through their ability to recognize -acetyl lysine (KAc) post-translational m...

Discovery of Potent, Reversible and Competitive Cruzain Inhibitors with Trypanocidal Activity: A Structure-Based Drug Design Approach.

A virtual screening conducted with nearly 4,000,000 compounds from lead-like and fragment-like subsets enabled the identification of a small-molecule inhibitor (1) of the Trypanosoma cruzi cruzain enz...

Solvent Screening in Zwitterions Analyzed with the Fragment Molecular Orbital Method.

Based on induced solvent charges, a new model of solvent screening is developed in the framework of the fragment molecular orbital combined with the polarizable continuum model. The developed model is...

Clinical Trials [9466 Associated Clinical Trials listed on BioPortfolio]

The TARGET-EFT Trial

Randomized clinical trial to determine whether a multicomponent intervention will lead to improvements in mobility, self-care, mood, pain, and physical activity among frail and pre-frail o...

The Happy Older Latinos Are Active (HOLA) Health Promotion Study in HIV-Infected Latino Men

The purpose of this study is to look at the best ways to prevent chronic diseases like diabetes, high blood pressure, and obesity in midlife and older Latino adults living with HIV. The in...

A Study Comparing the Efficacy and Safety of IDP-120 Gel in the Treatment of Acne Vulgaris

The primary objective of this study is to compare the efficacy, safety, and tolerability of IDP-120 Gel to IDP-120 Component A, IDP-120 Component B, and IDP-120 Vehicle Gel in subjects wit...

Evaluating Methods to Increase HIV Testing, Access to HIV Care, and HIV Prevention Strategies

This is a five-part study that will take place in the Bronx, NY, and Washington, D.C. The different components of the study will focus on increasing the number of people being tested for H...

Preventing Anxiety and Depression in Older Hispanics

The purpose of this study is to look at the best ways to prevent anxiety and depression in older Latino adults who are at risk for developing anxiety and depression. Participants will be r...

Medical and Biotech [MESH] Definitions

The identification of selected parameters in newborn infants by various tests, examinations, or other procedures. Screening may be performed by clinical or laboratory measures. A screening test is designed to sort out healthy neonates (INFANT, NEWBORN) from those not well, but the screening test is not intended as a diagnostic device, rather instead as epidemiologic.

Experience-based techniques for problem-solving, learning, and discovery that find a solution which is not guaranteed to be optimal, but sufficient for a given set of goals.

A process that searches for hidden and important connections among information embedded in published literature.

Techniques for separation and identification of ionized molecules based on their drift through a gas phase after being accelerated by an electric field. Their mobilities will be effected by their shape, size, and charge.

Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment.

Quick Search


DeepDyve research library

Relevant Topics

Nutrition
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Mergers & Acquisitions
Commercial and market reports on mergers and acquisitions in the biotechnology, pharmaceutical, medical device and life-science industries. Mergers and acquisitions (abbreviated M&A;) is an aspect of corporate strategy, corporate finance and manageme...


Searches Linking to this Article