Implications of protein flexibility for drug discovery.

by: SJ Teague

Nat Rev Drug Discov, Vol. 2, No. 7. (July 2003), pp. 527-541.

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Abstract

Proteins are in constant motion between different conformational states with similar energies. This has often been ignored in drug design. However, protein flexibility is fundamental to understanding the ways in which drugs exert biological effects, their binding-site location, binding orientation, binding kinetics, metabolism and transport. Protein flexibility allows increased affinity to be achieved between a drug and its target. This is crucial, because the lipophilicity and number of polar interactions allowed for an oral drug is limited by absorption, distribution, metabolism and toxicology considerations.

@article{citeulike:762080, abstract = {Proteins are in constant motion between different conformational states with similar energies. This has often been ignored in drug design. However, protein flexibility is fundamental to understanding the ways in which drugs exert biological effects, their binding-site location, binding orientation, binding kinetics, metabolism and transport. Protein flexibility allows increased affinity to be achieved between a drug and its target. This is crucial, because the lipophilicity and number of polar interactions allowed for an oral drug is limited by absorption, distribution, metabolism and toxicology considerations.}, address = {AstraZeneca R\&D Charnwood, Bakewell Road, Loughborough, Leicester LE11 5RH, UK. simon.teague@astrazeneca.com}, author = {Teague, S. J. }, citeulike-article-id = {762080}, doi = {10.1038/nrd1129}, issn = {1474-1776}, journal = {Nat Rev Drug Discov}, keywords = {discovery, drug}, month = {July}, number = {7}, pages = {527--541}, posted-at = {2006-08-01 14:41:40}, priority = {3}, title = {Implications of protein flexibility for drug discovery.}, url = {http://dx.doi.org/10.1038/nrd1129}, volume = {2}, year = {2003} }

RIS record

TY - JOUR ID - citeulike:762080 L3 - citeulike-article-id:762080 TI - Implications of protein flexibility for drug discovery. JF - Nat Rev Drug Discov VL - 2 IS - 7 SP - 527 EP - 541 AD - AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leicester LE11 5RH, UK. simon.teague@astrazeneca.com SN - 1474-1776 N2 - Proteins are in constant motion between different conformational states with similar energies. This has often been ignored in drug design. However, protein flexibility is fundamental to understanding the ways in which drugs exert biological effects, their binding-site location, binding orientation, binding kinetics, metabolism and transport. Protein flexibility allows increased affinity to be achieved between a drug and its target. This is crucial, because the lipophilicity and number of polar interactions allowed for an oral drug is limited by absorption, distribution, metabolism and toxicology considerations. KW - discovery KW - drug AU - Teague, SJ PY - 2003/07// UR - http://dx.doi.org/10.1038/nrd1129 ER -

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