BackgroundWeak intermolecular interactions such as hydrogen bonding and hydrophobic interactions are key players in stabilizing energetically-favored ligands, in an open conformational environment of protein structures. However, it is still poorly understood how the binding parameters associated with these interactions facilitate a drug-lead to recognize a specific target and improve drugs efficacy. To understand this, comprehensive analysis of hydrophobic interactions, hydrogen bonding and binding affinity have been analyzed at the interface of c-Src and c-Abl kinases and 4-amino substituted 1H-pyrazolo [3, 4-d] pyrimidine compounds.MethodologyIn-silico docking studies were performed, using Discovery Studio software modules LigandFit, CDOCKER and ZDOCK, to investigate the role of ligand binding affinity at the hydrophobic pocket of c-Src and c-Abl kinase. Hydrophobic and hydrogen bonding interactions of docked molecules were compared using LigPlot program. Furthermore, 3D-QSAR and MFA calculations were scrutinized to quantify the role of weak interactions in binding affinity and drug efficacy.ConclusionsThe in-silico method has enabled us to reveal that a multi-targeted small molecule binds with low affinity to its respective targets. But its binding affinity can be altered by integrating the conformationally favored functional groups at the active site of the ligand-target interface. Docking studies of 4-amino-substituted molecules at the bioactive cascade of the c-Src and c-Abl have concluded that 3D structural folding at the protein-ligand groove is also a hallmark for molecular recognition of multi-targeted compounds and for predicting their biological activity. The results presented here demonstrate that hydrogen bonding and optimized hydrophobic interactions both stabilize the ligands at the target site, and help alter binding affinity and drug efficacy.
This column supports the development of urgent pedagogies about climate justice learning in elementary and middle school ELA classrooms. In each issue, we will explore practical ways elementary teachers can engage young people to read, compose, learn about, and act on climate justice. In this issue, we explore how we reimagined a teacher book club to explore the urgent topic of climate justice, nourishing ourselves as PK-16 educators. Reimagining Teacher Book Clubs to Support Inquiry into Urgent TopicsInspired by Dr. Gholdy Muhammad's (2020) work, we have conceptualized urgent writing pedagogies as those that support youth to read, write, inquire into, and collaborate about meaningful topics that are responsive to the social times (Woodard & Schutz, in press). There are many such topics circulating in America today, including -as just some examples-racial injustice, mental health, gender equality, and gun control. Multidisciplinary inquiries into these kinds of topics can feel consequential and motivating to youth and support them to learn to read/analyze complex texts and communicate to varied audiences.Centering these topics in our curricula can also be fraught for teachers who are experiencing both unprecedented scrutiny from politicians and parents alike (Ujifusa, 2022) as well as heightened levels of burnout and chronic overwork (Chang et al., 2022). And yet, perhaps more than ever, we have felt the need to engage with our colleagues in work that feels meaningful and acknowledges and responds to today's challenges.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.