This work substantiates communication between the two binding pockets, the sustained use of combination therapy to treat HIV infection, and a molecular basis for understanding synergy. This inhibition is mediated through an effect on both the rate of the chemical step and binding of ATP, resulting in an overall decrease in efficiency of removal. The present study supports this hypothesis by illustrating that the clinically approved NNRTIs, nevirapine and efavirenz, inhibit the ATP-mediated removal of AZTMP, d4TMP, ddCMP, (-)3TCMP, (-)FTCMP, and (+)3TCMP, thereby prolonging the effectiveness of chain termination. Proposals will be evaluated on the sole criterion of scientific excellence which, in the case the ERC Synergy Grants, takes on the additional meaning of. (physiology) The cooperation of two or more nerves, muscles, organs, etc. This interplay between the two sites offers a plausible hypothesis for understanding synergy in which binding of NNRTIs modulates the chain termination by NRTIs. NounEdit (systems theory) A synonym of binding energy. This work also suggests communication between the two sites, since the inhibition of RT by NNRTIs is manifested through a remote effect on the chemical step. (1995) Science 267, 988-993) have shown that the natural deoxynucleoside triphosphate and the NNRTI can simultaneously bind to their respective sites.

the combination of common interests, common values, and complementary talents defines the potential for team. Previous mechanistic studies from our laboratory (Spence, R. in modern organizational theory, synergy means much more than working together. A general mechanism to define the molecular basis for synergy between these two classes remains to be elucidated. This synergy is observed within the two classes of inhibitors that target the essential viral reverse transcriptase (RT): the chain-terminating nucleoside analogs (NRTIs) and the allosteric nonnucleosides (NNRTIs) that bind in a pocket distinct from the active site. Partnership Synergy in Long-standing Equity-focused CBPR Partner- ships. Combination therapies treating human immunodeficiency virus type 1 (HIV-1) infection delay the emergence of drug-resistant virus and exhibit synergistic inhibition. A Participatory, Mixed Methods Approach to Define and Measure.

Define synergy