4D- quantitative structure-activity relationship modeling: making a comeback.

08:00 EDT 12th September 2019 | BioPortfolio

Summary of "4D- quantitative structure-activity relationship modeling: making a comeback."

: Predictive Quantitative Structure-Activity Relationship (QSAR) modeling has become an essential methodology for rapidly assessing various properties of chemicals. The vast majority of these QSAR models utilize numerical descriptors derived from the two- and/or three-dimensional structures of molecules. However, the conformation-dependent characteristics of flexible molecules and their dynamic interactions with biological target(s) is/are not encoded by these descriptors, leading to limited prediction performances and reduced interpretability. 2D/3D QSAR models are successful for virtual screening, but typically suffer at lead optimization stages. That is why conformation-dependent 4D-QSAR modeling methods were developed two decades ago. However, these methods have always suffered from the associated computational cost. Recently, 4D-QSAR has been experiencing a significant come-back due to rapid advances in GPU-accelerated molecular dynamic simulations and modern machine learning techniques. : Herein, the authors briefly review the literature regarding 4D-QSAR modeling and describe its modern workflow called MD-QSAR. Challenges and current limitations are also highlighted. : The development of hyper-predictive MD-QSAR models could represent a disruptive technology for analyzing, understanding, and optimizing dynamic protein-ligand interactions with countless applications for drug discovery and chemical toxicity assessment. Therefore, there has never been a better time and relevance for molecular modeling teams to engage in hyper-predictive MD-QSAR modeling.


Journal Details

This article was published in the following journal.

Name: Expert opinion on drug discovery
ISSN: 1746-045X
Pages: 1-9


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Medical and Biotech [MESH] Definitions

A quantitative prediction of the biological, ecotoxicological or pharmaceutical activity of a molecule. It is based upon structure and activity information gathered from a series of similar compounds.

The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.

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A characteristic showing quantitative inheritance such as SKIN PIGMENTATION in humans. (From A Dictionary of Genetics, 4th ed)

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