Dataset Information

Comparing Fragment Binding PosesPrediction Using HSP90 as a Key Study: When Bound Water Makes the Difference.

ABSTRACT: Fragment-Based Drug Discovery (FBDD) approaches have gained popularitynot only in industry but also in academic research institutes.However, the computational prediction of the binding mode adopted by fragment-like molecules within a protein binding site is still a very challenging task. One of the most crucial aspects of fragment binding is related to the large amounts of bound waters in the targeted binding pocket. The binding affinity of fragmentsmay not be sufficientto displace the bound water molecules. In the present work, we confirmed the importance of the bound water molecules in the correct prediction of the fragment binding mode.Moreover, we investigate whether the use of methods based on explicit solvent molecular dynamics simulations can improve the accuracy of fragment posing. The protein chosen for this study is HSP-90.

SUBMITTER: Bolcato G

PROVIDER: S-EPMC7587341 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Comparing Fragment Binding Poses Prediction Using HSP90 as a Key Study: When Bound Water Makes the Difference.

Bolcato Giovanni G Bissaro Maicol M Sturlese Mattia M Moro Stefano S

Molecules (Basel, Switzerland) 20201012 20

Fragment-Based Drug Discovery (FBDD) approaches have gained popularity not only in industry but also in academic research institutes. However, the computational prediction of the binding mode adopted by fragment-like molecules within a protein binding site is still a very challenging task. One of the most crucial aspects of fragment binding is related to the large amounts of bound waters in the targeted binding pocket. The binding affinity of fragments may not be sufficient to displace the bound ...[more]

PMID: 33053878

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Project description:BackgroundSupraventricular tachycardia is a group of rhythm disturbances that affect 1 in 300-1200 Australian children annually. The differentiation of supraventricular tachycardia (SVT) symptoms and age of onset according to their subtype is not well understood in the pediatric population. Most studies rely on ECG criteria only to characterize the subtype of the SVT, which is not applicable to all subtypes. The purpose of this study was to identify the symptoms and ages of onset of SVT subtypes, and to analyze whether ethnicity or severity correlated with the SVT subtype confirmed in an invasive Electrophysiology (EP) study.MethodsA retrospective analysis and prospective survey evaluated 364 patients who underwent an EP study at The Royal Children's Hospital, Melbourne between 2009 and 2015. Age of onset, symptoms, and ethnicity were collected by phone survey or medical records in addition to EP study diagnostic data, medication status, and follow-up information about their symptom status following EP procedure. Patients were grouped according to their SVT subtype. Data analysis was performed using chi-squared, Fisher's exact, and ANOVA statistical tests to determine associations between SVT substrates.ResultsTwo hundred and thirty-three suitable cases of SVT were identified (131 men, 102 women) aged between 0 and 18 years. Atrioventricular Reentrant Tachycardia (AVRT) (n = 153) was the most common SVT subtype, followed by Atrioventricular Nodal Reentrant Tachycardia (AVNRT) (n = 55), Atrial Tachycardia (AT) (n = 17), and other SVT subtypes (n = 8) which included Atrial Fibrillation, Atrial Flutter, and Junctional Tachycardia. There was a male predominance in all subtypes, except for AVNRT. AVNRT patients had palpitations, dyspnoea, dizziness, and anxiety more than any other group, AVRT patients complained of vomiting most and patients with AT had the most fatigue. The mean age of symptom onset varied among groups, being earlier in AVRT, later in AVNRT with a significant difference between AVRT with unidirectional retrograde accessory pathway (URAP) and AVNRT subtypes (P < 0.01).ConclusionSome specific symptoms were strong discriminators between different SVT subtypes. Ethnicity did not have strong correlations with SVT subtype incidence. This study was able to show clinical differences among children with SVT due to AVRT (URAP) compared to AVNRT, allowing the prognosis and intended management of pediatric SVT to be anticipated by less invasive means.

Dataset Information

Comparing Fragment Binding PosesPrediction Using HSP90 as a Key Study: When Bound Water Makes the Difference.

Publications

Comparing Fragment Binding Poses Prediction Using HSP90 as a Key Study: When Bound Water Makes the Difference.

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