A Structural and Functional View of Polypharmacology

نویسندگان

  • Aurelio A. Moya-Garcia
  • Natalie L. Dawson
  • Felix A. Kruger
  • John P. Overington
  • Christine Orengo
  • Juan A.G. Ranea
چکیده

The similarity property principle states that similar compounds have similar properties. In this study, we demonstrate that validity this principle holds well when the drug targets are protein domains. We leverage the similarity property principle to explore the druggability of CATH-FunFams, a type of protein domain and we use the associations between drugs and CATH-FunFams to explore drug polypharmacology by considering how the drugs’ pharmacological effects arise from the molecular targets they interact with. Our results demonstrate that drug protein interactions are mediated by drug-domain interactions and that CATH-FunFams provide a reasonable annotation level for drug-target interactions, opening a new research direction in target identification. . CC-BY 4.0 International license not peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/044289 doi: bioRxiv preprint first posted online Mar. 18, 2016;

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Insights into polypharmacology from drug-domain associations

MOTIVATION Polypharmacology (the ability of a single drug to affect multiple targets) is a key feature that may explain part of the decreasing success of conventional drug discovery strategies driven by the quest for drugs to act selectively on a single target. Most drug targets are proteins that are composed of domains (their structural and functional building blocks). RESULTS In this work, ...

متن کامل

Characterizing the pocketome of Mycobacterium tuberculosis and application in rationalizing polypharmacological target selection

Polypharmacology is beginning to emerge as an important concept in the field of drug discovery. However, there are no established approaches to either select appropriate target sets or design polypharmacological drugs. Here, we propose a structural-proteomics approach that utilizes the structural information of the binding sites at a genome-scale obtained through in-house algorithms to characte...

متن کامل

Structural insights into the polypharmacological activity of quercetin on serine/threonine kinases

Polypharmacology, the discovery or design of drug molecules that can simultaneously interact with multiple targets, is gaining interest in contemporary drug discovery. Serine/threonine kinases are attractive targets for therapeutic intervention in oncology due to their role in cellular phosphorylation and altered expression in cancer. Quercetin, a naturally occurring flavonoid, inhibits multipl...

متن کامل

Curation and Analysis of Multitargeting Agents for Polypharmacological Modeling

In drug discovery and development, the conventional "single drug, single target" concept has been shifted to "single drug, multiple targets"--a concept coined as polypharmacology. For studies in this emerging field, dedicated and high-quality databases of multitargeting ligands would be exceedingly beneficial. To this end, we conducted a comprehensive analysis of the structural and chemical/bio...

متن کامل

Assessment of safety status and functional, structural and non-structural preparedness of health centers in Hamadan against disasters

Background: The most important demand of people in disasters is health and the provision of coordinated, integrated, continuous, and accessible health services. Effective disaster management depends on anticipating and identifying disaster problems and considering the necessary facilities. The aim of this study was to evaluate the safety status and functional, structural, and non-structural pre...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2016