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world:biochemistry [2018/03/21 09:09] (current)
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 +====== Rational Drug Design by ‚Ä®Modeling the Protein-Drug Interactions ======
  
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 +Drug discovery by Pharma and others often employs a brute-force approach where hundreds and thousands of molecules are tested as drug candidates for inhibition of the function of a protein responsible for a disease. This approach is not only cost prohibitive but has met with very limited success, and this problem is further exacerbated in cases where a disease is classified as orphan disease because the investment required to find a cure is not financially viable for pharmaceutical industries. However, the chemical space of drug candidates can be greatly reduced by using an in silico approach where the structure of the functional pocket can be modeled using a homology modeling (aided by experimental NMR or X-ray crystallography structures of proteins with similar primary sequence of amino acids), and then the molecular docking simulations can be used to find the molecules that fit that pocket and allow for favorable non-covalent interactions. Furthermore,​ one could use the molecular dynamics simulations to obtain valuable information about the specific mechanism of action of the active pocket, which is necessary for guiding the design of potential drugs that will inhibit only a desired enzyme. ​
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 +The most promising candidates can be used for the experimental screening, and the experimental feedback can be reused in the in silico modeling to generate the next-generation candidates. This research program aims to utilize this approach for the development of a drug for treatment of orphan disease called infantile hemangioma. As numerous drug-development studies could benefit from this approach, we will expand this successfully approbated methodology to other diseases and, ultimately, look into development of a robust protocol for spotting and employing unique features of the catalytic domains of proteins for developments of highly specific drugs that would target only the desired enzyme.
world/biochemistry.txt · Last modified: 2018/03/21 09:09 (external edit)