Topics

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.

Affiliation

Journal Details

This article was published in the following journal.

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

Links

DeepDyve research library

PubMed Articles [28448 Associated PubMed Articles listed on BioPortfolio]

An integrated quantitative structure and mechanism of action-activity relationship model of human serum albumin binding.

Traditional quantitative structure-activity relationship models usually neglect the molecular alterations happening in the exposed systems (the mechanism of action, MOA), that mediate between structur...

Molecular modeling approaches for the discovery of adenosine A receptor antagonists: current status and future perspectives.

Adenosine receptors (ARs) are classified as A, A, A, and A subtypes belonging to the superfamily of G-protein-coupled receptors (GPCRs). Several molecular modeling approaches have been developed for A...

Quantitative Structure-Property Relationship Approach in Formulation Development: an Overview.

Chemoinformatics is emerging as a new trend to set drug discovery which correlates the relationship between structure and biological functions. The main aim of chemoinformatics refers to analyzing the...

Structure-Activity Relationship of Iron Oxides for NO reduction in the presence of C₃H₆, CO, and O₂.

Spinel-type NiFe₂O₄ exhibited the highest NO reduction activity among base metal oxides under simulated exhaust of gasoline vehicle. We investigated the structure-activity relationship of iron oxi...

Discovery of HWL-088: A highly potent FFA1/GPR40 agonist bearing a phenoxyacetic acid scaffold.

Based on a previously reported phenoxyacetic acid scaffold, compound 7 (HWL-088) has been identified as a superior free fatty acid receptor 1 (FFA1) agonist by comprehensive structure-activity relatio...

Clinical Trials [8907 Associated Clinical Trials listed on BioPortfolio]

Computer Modeling of Congenital Heart Disease

This proposal is aimed at developing a novel method for modeling and analyzing clinical factors impacting RV function, which can lead to a more reliable, consistent, and comprehensive pre-...

Social Decision-making

The purpose of this study is to investigate neural mechanism of healthy humans underlying group decision making and compare it with that of individual decision-making. Using functional neu...

The Effects of Video Modeling of Audiological Testing on Pediatric Patient Compliance

The purpose of the current study is to determine if pre-exposure through video modeling will enhance testing compliance in a population of children who are receiving a diagnostic evaluatio...

Brain Genomics Superstruct Project

The purpose of this study is to explore the effects of genes and genetic variation on brain structure and function. Investigators at Harvard plan to explore the relationship between candid...

Semi-automatic assessMent of Aortic Roots by Three-dimensional transoEsophageal echocaRdiography (SMARTER)

The progress in surgery of the aortic root and the evolution of transcatheter aortic valve replacement as an alternative to surgical treatment in selected patients have refocused the need ...

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.

Locations, on the GENOME, of GENES or other genetic elements that encode or control the expression of a quantitative trait (QUANTITATIVE TRAIT, HERITABLE).

The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.

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

Quick Search


DeepDyve research library

Relevant Topics

Biological Therapy
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...

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...


Searches Linking to this Article