Novel computational biology methods and their applications to drug discovery

doi:10.1007/s11515-011-1125-7

Front Biol

2011, Vol. 6

Issue (4) : 289-299 https://doi.org/10.1007/s11515-011-1125-7

REVIEW

Novel computational biology methods and their applications to drug discovery

Sharangdhar S. PHATAK^1,2, Hoang T. TRAN², Shuxing ZHANG²(

)

1. School of Biomedical Informatics, The University of Texas Health Science Center, 7000 Fannin Street, Houston, TX 77030, USA; 2. The Integrated Molecular Discovery Laboratory, Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA

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Abstract

Computational biology methods are now firmly entrenched in the drug discovery process. These methods focus on modeling and simulations of biological systems to complement and direct conventional experimental approaches. Two important branches of computational biology include protein homology modeling and the computational biophysics method of molecular dynamics. Protein modeling methods attempt to accurately predict three-dimensional (3D) structures of uncrystallized proteins for subsequent structure-based drug design applications. Molecular dynamics methods aim to elucidate the molecular motions of the static representations of crystallized protein structures. In this review we highlight recent novel methodologies in the field of homology modeling and molecular dynamics. Selected drug discovery applications using these methods conclude the review.

Keywords computational biology drug discovery homology modeling molecular dynamics structure-based drug design

Corresponding Author(s): ZHANG Shuxing,Email:shuzhang@mdanderson.org

Issue Date: 01 August 2011

Cite this article:

Sharangdhar S. PHATAK,Hoang T. TRAN,Shuxing ZHANG. Novel computational biology methods and their applications to drug discovery[J]. Front Biol, 2011, 6(4): 289-299.

URL:

https://academic.hep.com.cn/fib/EN/10.1007/s11515-011-1125-7
https://academic.hep.com.cn/fib/EN/Y2011/V6/I4/289

Fig.1 A representative workflow for protein modeling methods

Fig.2 Cannabinoid receptor 2 complexed with N-alkyl-isatin acylhydrazone derivative (yellow carbon atoms) identified through protein homology modeling and structure-based library screening. Transmembrane regions are shown as white ribbons. Hydrogen bonds are represented as red dashes.

Tab.1 Examples of applications of protein modeling to drug discovery and development.

Fig.3 An example of using molecular dynamics to generate an ensemble of alternative receptor-ligand structures. Ten structures generated using molecular dynamics of the pleckstrin homology domain of protein kinase B (blue cartoon display) complexed with inositol 1,3,4,5-tetrakisphosphate (wire display) are shown.

Tab.2 Applications of molecular dynamics to drug discovery and development

Fig.4 The generic strategy of using molecular dynamics simulations to generate alternative docking poses.

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