Awol Hussen, Arebu Hussen
Influence of Small-Scale Irrigation on Livelihoods of Rural Farm Households in the Case of Legehida District, Ethiopia
TheScientificWorldJournal
function proteins biological nanomachines relies ability fold complex 3d structures bind selectively partners undergo conformational changes cue native functional structures rates interconversion conformational states foldedunfolded boundfree encoded physical chemistry amino acid sequence however despite extensive research decades code proven difficult fully crack terms prediction understanding molecular mechanisms playearlier work singledomain proteins reported commonality slow rates 102102 s1 simple behavior kinetic thermodynamic unfolding experiments suggested process allornone thereby analogous chemical reaction eg b absence firstprinciples preexponential factor protein unfolding dynamics rates could interpreted relative terms eg changes induced mutation hence neither height entropic contribution free energy barriers known rates also many orders magnitude slow direct atomistic simulations computational focus predicting rate changes induced mutation via coarse grained simulations however even effects mutation proved strikingly homogeneous experimental data clustering 13 free energy perturbation recovered folding 23 unfoldingthe implementation ultrafast kinetic methods turned field upside allowed researchers measure time scales elementary unfolding motions set preexponential factor protein conformational transitions 1 parallel others set investigate simplest possible protein structures capable autonomous folding defined archetypal folds rationale recapitulate hierarchical organization protein structure starting bottom study fold archetypes ended opening new research avenues protein unfolding also making unexpected connections folding upon binding intrinsically disordered proteins suggesting functioning conformational rheostatsthis account describes work kinetic thermodynamic mechanistic functional analysis fold archetypes first discuss kinetic studies emphasizing impact understanding unfolding rates barrierless downhill folding benchmarks atomistic simulations continue thermodynamic analysis introducing differential scanning calorimetry multiprobe nmr approaches developed dissect gradual minimally cooperative unfolding transitions probe underlying mechanisms unprecedented detail last two sections cover singlemolecule analyses recent mostly computational results exploration possible biological technological roles gradual conformational transitions fold archetypes