Fine tuning for success in structure-based virtual screening

2021 ◽  
Author(s):  
Emilie Pihan ◽  
Martin Kotev ◽  
Obdulia Rabal ◽  
Claudia Beato ◽  
Constantino Diaz Gonzalez
Keyword(s):  
Virtual Screening ◽  
Fine Tuning

scholarly journals TranScreen: Transfer Learning on Graph-Based Anti-Cancer Virtual Screening Model

2020 ◽  
Vol 4 (3) ◽  
pp. 16
Author(s):  
Milad Salem ◽  
Aminollah Khormali ◽  
Arash Keshavarzi Arshadi ◽  
Julia Webb ◽  
Jiann-Shiun Yuan
Keyword(s):  
Virtual Screening ◽  
Transfer Learning ◽  
Fine Tuning ◽  
Superior Performance ◽  
Receiver Operating Curve ◽  
Target Task ◽  
Automatic Feature Extraction ◽  
Unseen Data ◽  
Anti Cancer ◽  
Multiple Challenges

Deep learning’s automatic feature extraction has proven its superior performance over traditional fingerprint-based features in the implementation of virtual screening models. However, these models face multiple challenges in the field of early drug discovery, such as over-training and generalization to unseen data, due to the inherently unbalanced and small datasets. In this work, the TranScreen pipeline is proposed, which utilizes transfer learning and a collection of weight initializations to overcome these challenges. An amount of 182 graph convolutional neural networks are trained on molecular source datasets and the learned knowledge is transferred to the target task for fine-tuning. The target task of p53-based bioactivity prediction, an important factor for anti-cancer discovery, is chosen to showcase the capability of the pipeline. Having trained a collection of source models, three different approaches are implemented to compare and rank them for a given task before fine-tuning. The results show improvement in performance of the model in multiple cases, with the best model increasing the area under receiver operating curve ROC-AUC from 0.75 to 0.91 and the recall from 0.25 to 1. This improvement is vital for practical virtual screening via lowering the false negatives and demonstrates the potential of transfer learning. The code and pre-trained models are made accessible online.

Fine-Tuning Futures

ASHA Leader ◽  
2017 ◽  
Vol 22 (6) ◽  
Author(s):  
Christi Miller
Keyword(s):  
Fine Tuning

Food Safety Security: A new Concept for Enhancing Food Safety Measures

2012 ◽  
Vol 82 (3) ◽  
pp. 216-222 ◽  
Author(s):  
Venkatesh Iyengar ◽  
Ibrahim Elmadfa
Keyword(s):  
Food Safety ◽  
Hazard Analysis ◽  
Warning System ◽  
Shared Responsibility ◽  
Fine Tuning ◽  
Strategic Action ◽  
Surveillance Network ◽  
Measurement Systems ◽  
Critical Control Points ◽  
The Impact

The food safety security (FSS) concept is perceived as an early warning system for minimizing food safety (FS) breaches, and it functions in conjunction with existing FS measures. Essentially, the function of FS and FSS measures can be visualized in two parts: (i) the FS preventive measures as actions taken at the stem level, and (ii) the FSS interventions as actions taken at the root level, to enhance the impact of the implemented safety steps. In practice, along with FS, FSS also draws its support from (i) legislative directives and regulatory measures for enforcing verifiable, timely, and effective compliance; (ii) measurement systems in place for sustained quality assurance; and (iii) shared responsibility to ensure cohesion among all the stakeholders namely, policy makers, regulators, food producers, processors and distributors, and consumers. However, the functional framework of FSS differs from that of FS by way of: (i) retooling the vulnerable segments of the preventive features of existing FS measures; (ii) fine-tuning response systems to efficiently preempt the FS breaches; (iii) building a long-term nutrient and toxicant surveillance network based on validated measurement systems functioning in real time; (iv) focusing on crisp, clear, and correct communication that resonates among all the stakeholders; and (v) developing inter-disciplinary human resources to meet ever-increasing FS challenges. Important determinants of FSS include: (i) strengthening international dialogue for refining regulatory reforms and addressing emerging risks; (ii) developing innovative and strategic action points for intervention {in addition to Hazard Analysis and Critical Control Points (HACCP) procedures]; and (iii) introducing additional science-based tools such as metrology-based measurement systems.

Fine-Tuning Sought for Monitoring Celiac Disease Patients

2008 ◽  
Vol 38 (11) ◽  
pp. 30
Author(s):  
KATE JOHNSON
Keyword(s):  
Celiac Disease ◽  
Fine Tuning

Search for cannabinoid receptor 1 antagonists using structure-based virtual screening: identification of natural product hits

Planta Medica ◽  
2014 ◽  
Vol 80 (10) ◽  
Author(s):  
P Pandey ◽  
KK Roy ◽  
H Liu ◽  
KM Elokely ◽  
S Pettaway ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Natural Product ◽  
Cannabinoid Receptor ◽  
Cannabinoid Receptor 1

Imaginings

2017 ◽  
Vol 9 (3) ◽  
pp. 17-30
Author(s):  
Kelly James Clark
Keyword(s):  
Religious Tradition ◽  
Second Order ◽  
Fine Tuning ◽  
Intellectual Humility ◽  
First Order ◽  
Natural Processes ◽  
Empirically Supported ◽  
Group Violence ◽  
The World ◽  
The Universe

In Branden Thornhill-Miller and Peter Millican’s challenging and provocative essay, we hear a considerably longer, more scholarly and less melodic rendition of John Lennon’s catchy tune—without religion, or at least without first-order supernaturalisms (the kinds of religion we find in the world), there’d be significantly less intra-group violence. First-order supernaturalist beliefs, as defined by Thornhill-Miller and Peter Millican (hereafter M&M), are “beliefs that claim unique authority for some particular religious tradition in preference to all others” (3). According to M&M, first-order supernaturalist beliefs are exclusivist, dogmatic, empirically unsupported, and irrational. Moreover, again according to M&M, we have perfectly natural explanations of the causes that underlie such beliefs (they seem to conceive of such natural explanations as debunking explanations). They then make a case for second-order supernaturalism, “which maintains that the universe in general, and the religious sensitivities of humanity in particular, have been formed by supernatural powers working through natural processes” (3). Second-order supernaturalism is a kind of theism, more closely akin to deism than, say, Christianity or Buddhism. It is, as such, universal (according to contemporary psychology of religion), empirically supported (according to philosophy in the form of the Fine-Tuning Argument), and beneficial (and so justified pragmatically). With respect to its pragmatic value, second-order supernaturalism, according to M&M, gets the good(s) of religion (cooperation, trust, etc) without its bad(s) (conflict and violence). Second-order supernaturalism is thus rational (and possibly true) and inconducive to violence. In this paper, I will examine just one small but important part of M&M’s argument: the claim that (first-order) religion is a primary motivator of violence and that its elimination would eliminate or curtail a great deal of violence in the world. Imagine, they say, no religion, too.Janusz Salamon offers a friendly extension or clarification of M&M’s second-order theism, one that I think, with emendations, has promise. He argues that the core of first-order religions, the belief that Ultimate Reality is the Ultimate Good (agatheism), is rational (agreeing that their particular claims are not) and, if widely conceded and endorsed by adherents of first-order religions, would reduce conflict in the world.While I favor the virtue of intellectual humility endorsed in both papers, I will argue contra M&M that (a) belief in first-order religion is not a primary motivator of conflict and violence (and so eliminating first-order religion won’t reduce violence). Second, partly contra Salamon, who I think is half right (but not half wrong), I will argue that (b) the religious resources for compassion can and should come from within both the particular (often exclusivist) and the universal (agatheistic) aspects of religious beliefs. Finally, I will argue that (c) both are guilty, as I am, of the philosopher’s obsession with belief. 

Discovery of Antibacterial Agents Inhibiting the Energy-Coupling Factor (ECF) Transporters by Structure-Based Virtual Screening

2020 ◽  
Author(s):  
Eleonora Diamanti ◽  
Inda Setyawati ◽  
Spyridon Bousis ◽  
leticia mojas ◽  
lotteke Swier ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Antibacterial Agents ◽  
Antimicrobial Agents ◽  
Energy Coupling ◽  
Coupling Factor ◽  
Design Synthesis ◽  
Screening Design ◽  
Starting Point ◽  
Wide Range ◽  
Vitamin Uptake

Here, we report on the virtual screening, design, synthesis and structure–activity relationships (SARs) of the first class of selective, antibacterial agents against the energy-coupling factor (ECF) transporters. The ECF transporters are a family of transmembrane proteins involved in the uptake of vitamins in a wide range of bacteria. Inhibition of the activity of these proteins could reduce the viability of pathogens that depend on vitamin uptake. Because of their central role in the metabolism of bacteria and their absence in humans, ECF transporters are novel potential antimicrobial targets to tackle infection. The hit compound’s metabolic and plasma stability, the potency (20, MIC Streptococcus pneumoniae = 2 µg/mL), the absence of cytotoxicity and a lack of resistance development under the conditions tested here suggest that this scaffold may represent a promising starting point for the development of novel antimicrobial agents with an unprecedented mechanism of action.<br>

Investigation of Au SAMs Photoclick Derivatization by PM-IRRAS

2019 ◽  
Author(s):  
Mark Workentin ◽  
François Lagugné-Labarthet ◽  
Sidney Legge
Keyword(s):  
Cell Adhesion ◽  
Self Assembly ◽  
Materials Science ◽  
Fibroblast Cell ◽  
Fine Tuning ◽  
Chemical System ◽  
Infrared Reflection ◽  
Assembled Monolayers ◽  
One Step ◽  
High Degree

In this work we present a clean one-step process for modifying headgroups of self-assembled monolayers (SAMs) on gold using photo-enabled click chemistry. A thiolated, cyclopropenone-caged strained alkyne precursor was first functionalized onto a flat gold substrate through self-assembly. Exposure of the cyclopropenone SAM to UV-A light initiated the efficient photochemical decarbonylation of the cyclopropenone moiety, revealing the strained alkyne capable of undergoing the interfacial strain-promoted alkyne-azide cycloaddition (SPAAC). Irradiated SAMs were derivatized with a series of model azides with varied hydrophobicity to demonstrate the generality of this chemical system for the modification and fine-tuning of the surface chemistry on gold substrates. SAMs were characterized at each step with polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS) to confirm successful functionalization and reactivity. Furthermore, to showcase the compatibility of this approach with biochemical applications, cyclopropenone SAMs were irradiated and modified with azide-bearing cell adhesion peptides to promote human fibroblast cell adhesion, then imaged by live cell fluorescence microscopy. Thus, the “photoclick” methodology reported here represents an improved, versatile, catalyst-free protocol that allows for a high degree of control over the modification of material surfaces, with applicability in materials science as well as biochemistry.<br>

Sign in / Sign up

Export Citation Format

Share Document