Fast protein folding on downhill energy landscape.
نویسندگان
چکیده
Proteins fold in a time range of microseconds to minutes despite the large amount of possible conformers. Molecular dynamics simulations of a three-stranded antiparallel beta-sheet peptide (for a total of 12.6 microsec and 72 folding events) show that at the melting temperature the unfolded state ensemble contains many more conformers than those sampled during a folding event.
منابع مشابه
Energy Landscape of All-Atom Protein-Protein Interactions Revealed by Multiscale Enhanced Sampling
Protein-protein interactions are regulated by a subtle balance of complicated atomic interactions and solvation at the interface. To understand such an elusive phenomenon, it is necessary to thoroughly survey the large configurational space from the stable complex structure to the dissociated states using the all-atom model in explicit solvent and to delineate the energy landscape of protein-pr...
متن کاملEngineering Folding Dynamics from Two-State to Downhill: Application to λ-Repressor
One strategy for reaching the downhill folding regime, primarily exploited for the λ(6-85) protein fragment, consists of cumulatively introducing mutations that speed up folding. This is an experimentally demanding process where chemical intuition usually serves as a guide for the choice of amino acid residues to mutate. Such an approach can be aided by computational methods that screen for pro...
متن کاملWhen fast is better: protein folding fundamentals and mechanisms from ultrafast approaches
Protein folding research stalled for decades because conventional experiments indicated that proteins fold slowly and in single strokes, whereas theory predicted a complex interplay between dynamics and energetics resulting in myriad microscopic pathways. Ultrafast kinetic methods turned the field upside down by providing the means to probe fundamental aspects of folding, test theoretical predi...
متن کاملProbing the folding free energy landscape of the Src-SH3 protein domain.
The mechanism and thermodynamics of folding of the Src homology 3 (SH3) protein domain are characterized at an atomic level through molecular dynamics with importance sampling. This methodology enables the construction of the folding free energy landscape of the protein as a function of representative reaction coordinates. We observe that folding proceeds in a downhill manner under native condi...
متن کاملDistinguishing between cooperative and unimodal downhill protein folding.
Conventional cooperative protein folding invokes discrete ensembles of native and denatured state structures in separate free-energy wells. Unimodal noncooperative ("downhill") folding, however, proposes an ensemble of states occupying a single free-energy well for proteins folding at >/=4 x 10(4) s(-1) at 298 K. It is difficult to falsify unimodal mechanisms for such fast folding proteins by s...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Protein science : a publication of the Protein Society
دوره 12 8 شماره
صفحات -
تاریخ انتشار 2003