Literatura académica sobre el tema "Hammond’s postulate"

An unfolded protein under favorable conditions navigates its complex energy landscape on a time scale of milliseconds to seconds and folds into a specific three dimensional structure. The mechanism of protein folding is affected by multiple factors such as temperature, pressure, pH and co-solvents. In this thesis using coarse-grained protein models and molecular dynamics simulations, I have studied various aspects of cosolvent induced protein folding. I have specifically addressed problems related to the early stages of protein folding, transient intermediates populated in the folding pathway and salt effects on protein folding thermodynamics. Proteins, which are finite sized heteropolymers are believed to undergo a coil-globule transition similar to polymers during the early stages of folding. However, single molecule fluorescence resonance energy transfer (FRET) and small angle X-ray scattering (SAXS) experiments studying coil-globule transition arrived at qualitatively different conclusions. Using computer simulations we have found that finite size proteins do exhibit small compaction on dilution of denaturant concentration. The FRET experiments overestimated the compaction due to approximating the protein as a Gaussian polymer chain, whereas the small compaction observed is within the statistical uncertainty of the SAXS experiments leading to the controversy. The protein compaction during the early stages of folding can be either specific or non-specific. The specific compaction in protein is due to the formation of a few native-like long ranged contacts in the protein during the early stages of folding. SAXS experiments on the protein monellin predicted that the compaction in this protein is specific. Using simulations, we have shown that the formation of a few native-like contacts in the β-strands of the proteins can lead to ∼ 17% compaction in the protein dimensions. We have also developed a computational model to predict the salt effects on the folding thermodynamics of proteins. Using lac-DBD and NTL9 as model systems we studied the effect of 7 different salts on their folding thermodynamics. I made several predictions, which can be verified by experiments on salt effects on the protein size in the denatured ensemble, and the subtle structural changes in the protein transition state ensemble, which are in line with the Hammond’s postulate. Recent FRET experiments on small globular proteins widely believed to be two-state folders have shown evidence for the population of transiently populated protein intermediate states. Using simulations, we studied the folding of protein L, and resolved the structure of a transient intermediate populated in its folding pathway