Integrated computational approaches and tools for allosteric drug discovery:

Amamuddy, Olivier S; Veldman, Wade; Manyumwa, Colleen; Khairallah, Afrah; Agajanian, Steve; Oluyemi, Odeyemi; Verkhivker, Gennady M; Tastan Bishop, Özlem

Title: Integrated computational approaches and tools for allosteric drug discovery:
Creator: Amamuddy, Olivier S
Creator: Veldman, Wade
Creator: Manyumwa, Colleen
Creator: Khairallah, Afrah
Creator: Agajanian, Steve
Creator: Oluyemi, Odeyemi
Creator: Verkhivker, Gennady M
Creator: Tastan Bishop, Özlem
Date Issued: 2020
Date: 2020
Type: text
Type: article
Identifier: http://hdl.handle.net/10962/163012
Identifier: vital:41004
Identifier: https://doi.org/10.3390/ijms21030847
Description: Understanding molecular mechanisms underlying the complexity of allosteric regulation in proteins has attracted considerable attention in drug discovery due to the benefits and versatility of allosteric modulators in providing desirable selectivity against protein targets while minimizing toxicity and other side effects. The proliferation of novel computational approaches for predicting ligand–protein interactions and binding using dynamic and network-centric perspectives has led to new insights into allosteric mechanisms and facilitated computer-based discovery of allosteric drugs. Although no absolute method of experimental and in silico allosteric drug/site discovery exists, current methods are still being improved. As such, the critical analysis and integration of established approaches into robust, reproducible, and customizable computational pipelines with experimental feedback could make allosteric drug discovery more efficient and reliable. In this article, we review computational approaches for allosteric drug discovery and discuss how these tools can be utilized to develop consensus workflows for in silico identification of allosteric sites and modulators with some applications to pathogen resistance and precision medicine. The emerging realization that allosteric modulators can exploit distinct regulatory mechanisms and can provide access to targeted modulation of protein activities could open opportunities for probing biological processes and in silico design of drug combinations with improved therapeutic indices and a broad range of activities.
Format: 40 pages
Format: pdf
Language: English
Relation: International Journal of Molecular Sciences
Relation: Sheik Amamuddy, O., Veldman, W., Manyumwa, C., Khairallah, A., Agajanian, S., Oluyemi, O., Verkhivker, G.M. and Tastan Bishop, Ö., 2020. Integrated computational approaches and tools for allosteric drug discovery. International Journal of Molecular Sciences, 21(3), p.847
Relation: International Journal of Molecular Sciences volume 21 number 3 1 39 January 2020 1422-0067
Rights: Publisher
Rights: Use of this resource is governed by the terms and conditions of the MDPI Open Access Statement (https://www.int-res.com/journals/terms-of-use/)

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Tastan Bishop, Ozlem (Prof)

RU Research Unit in Bioinformatics (RUBi)

RU Department of Biochemistry, Microbiology and Biotechnology

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